JP2008500846A - Method and product for making a grid of EMR-treated isolated points in tissue and use thereof - Google Patents

Abstract

The present invention relates to processing of tissue with electromagnetic radiation that creates a grid of isolated points (islets) processed with electromagnetic radiation (EMR) in the tissue. The present invention also relates to a device and system for creating a grid of isolated points that have been EMR processed in tissue, and to the cosmetic and medical applications of these devices and systems.
Disclosed is a method of processing tissue using electromagnetic radiation to create EMR processing isolated points in the tissue. Further disclosed are devices and systems for creating grids of EMR-treated isolated points in tissue, and the cosmetic and medical applications of such devices and systems.
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Description

  The invention relates to the treatment of tissue with electromagnetic radiation that creates a grid of electromagnetic radiation (EMR) treated islets within the tissue. The invention also relates to devices and systems for creating a grid of EMR-processed isolated points in tissue, and the cosmetic and medical applications of such devices and systems.

Related Applications This application is filed with US Provisional Application No. 60 / 561,052 filed on April 9, 2004, US Provisional Application No. 60 / 614,382 filed September 29, 2004, and January 5, 2005. Claimed benefit of US provisional application 60 / 614,616 filed; US filed June 19, 2003 claiming priority of US provisional application 60 / 389,871 filed June 19, 2002 US patent filed Dec. 27, 2001, which is a continuation-in-part of patent application No. 10 / 465,137; claiming priority of US Provisional Application No. 60 / 258,855 filed Dec. 28, 2000 US patent filed February 22, 2002, which is a continuation-in-part of application 10 / 033,302; and claims the priority of US Provisional Application No. 60 / 272,745 filed March 2, 2001 This is a continuation-in-part of Application No. 10 / 080,652.

  Electromagnetic radiation, particularly in the form of laser light, is used in various cosmetic and medical applications including dermatology, dentistry, ophthalmology, gynecology, otolaryngology and internal medicine. For most dermatological applications, EMR treatment can be performed using a device that delivers EMR to the surface of the target tissue. In internal medicine applications, it is common for EMR processing to deliver EMR to the inner surface and tissue using a device that works in conjunction with an endoscope or catheter. In general, EMR treatment consists of (a) delivering one or more specific wavelengths (or specific continuous wavelength regions) of EMR to the tissue to induce a specific chemical reaction, and (b) transferring EMR energy to the tissue. Or (c) designed to deliver EMR energy to tissue to damage or destroy cells or extracellular structures.

  Until recently, the application of radiant heat of light to medicine was all based on one of these three methods. The first method, known as the principle of selective photothermal, involves the wavelength used (required to be absorbed exclusively by the chromophore in the target region) and the length of the light pulse (rather than the thermal decay time specific to the target region). There are special requirements for short). This method has since been extended, often referred to as selective photothermal expansion theory, to include situations where the target region and target chromophore are physically separated. The second method relies on thermal diffusion from the target chromophore to the target area. The third method relies on absorption by a chromophore (eg, water) that is substantially uniformly present in the tissue. In this last example, the damage zone is controlled in principle by manipulating wavelength, fluence, incident beam size, pulse width and cooling parameters. All three methods have drawbacks, the biggest drawback being that it is difficult to eliminate unwanted side effects. Usually, the primary absorption of light energy by water causes significant tissue damage.

  Typical applications of photodermatology include the treatment of skin color abnormalities (skin tone) and skin remodeling. Standard methods of treating skin color abnormalities utilize the selective absorption of light by melanin in pigmented lesions or hemoglobin in blood vessels. Such treatment uses arc discharge lamps that are subjected to a plurality of lasers and spectroscopic filtering. Usually, the endpoint of treatment is clotting of blood vessels and pigmented lesions. Thermal stress on these targets collapses the blood vessels and kills them, and also places the pigmented lesions on the scab, after which the dead skin is peeled off. In both cases, skin tone improves, but skin remodeling is a side effect of these treatments because heat stress on the tissues surrounding blood vessels and pigmented lesions can stimulate new collagen production. May happen. Such therapeutic applications are generally safe because their damage is limited to small structures such as blood vessels and melanin-containing spots.

  One problem with selective photothermal decomposition is that the wavelength selected for radiation is generally determined by the absorption properties of the chromophore and may not be optimal for other purposes. Although skin is a scattering medium, such scattering is greater at certain wavelengths compared to other wavelengths. Unfortunately, for example, the wavelength that melanin exclusively absorbs is also the wavelength at which substantial scattering occurs. This is also true for wavelengths commonly used in the treatment of vascular injury. Skin photon absorption also varies throughout the visible wavelength range, and some wavelengths commonly used for selective photothermal decomposition are wavelengths where the skin exhibits strong absorption. The fact that the wavelengths commonly used for selective photopyrolysis are strongly scattered and / or strongly absorbed limits the ability to selectively target body components, especially for effective and efficient treatment. Limit the depth you can. In addition, much of the energy applied to the target area is scattered or absorbed by the tissue that does not reach, covers, or surrounds the body part being treated. This low efficiency for such treatments means that a larger and more powerful EMR source is needed to achieve the desired treatment outcome. However, the increase in power generally leads to undesirable and potentially dangerous tissue heating. Thus, increasing efficiency often reduces safety and additional costs and energy must be used to mitigate the effects of this undesirable tissue heating by surface cooling or other suitable techniques. Stronger EMR source thermal management is also a problem and generally requires expensive and bulky water circulation or other thermal management mechanisms. For these reasons, techniques that allow for efficient power levels and minimize unwanted heating are desired.

  Light skin treatments vary greatly in the concentration of chromophores in the target (eg, melanin in the hair follicle) between targets and patients, and are optimal parameters that are effective for treating a target, or even appropriate parameters It makes photo skin treatment more difficult because it makes it difficult to decide. Certain skins, such as those of individuals with dark skin or very tanned, are highly absorbed, making certain treatments difficult or even impossible to perform safely. For this reason, there is a need for a technique that can safely treat skin of any type and pigment, preferably with little or no pain, and preferably using substantially the same parameters.

Absorption of light energy by water is one of two methods for skin remodeling: exfoliative skin abrasion, typically performed manually using a CO ₂ (10.6μ) or Er: YAG (2.94μ) laser. Using a combination of deep skin heating with Nd: YAG (1.34μ), Er: glass (1.56μ) or diode laser (1.44μ) light and cooling of the skin surface for selective damage to the subepithelial tissue Widely used for non-peeling skin remodeling. In both cases, however, the healing reaction of the body begins as a result of limited thermal damage and ultimately results in the formation of new collagen and modification of the skin collagen / elastin matrix. These changes themselves appear in smoothing by crust resection and generally improve the appearance and feel of the skin (often referred to as “skin rejuvenation”). The main difference between the two technologies is the body area where damage begins. In ablation, the entire width of the epithelium and some upper dermis are excised and / or coagulated. In the non-exfoliating method, the coagulation zone moves to deeper tissue and the epithelium remains intact. In practice, this different wavelengths: very shallow penetration wavelength in peeling technique (absorption coefficient of CO ₂ and Er.YAG wavelength ～900Cm ^-1 and ～13000Cm ^-1 for respectively), and deeper in the non ablative therapy This is achieved using a penetration wavelength (absorption coefficient between 5 and 25 cm ^-1 ). In addition, in non-exfoliating techniques, the skin surface is contacted or spray cooled to protect the epithelium from heat. Exfoliation techniques have demonstrated significantly higher clinical effectiveness. In recent years, one drawback that has greatly limited the acceptance of this treatment is the need for continued care for a long time after surgery. Non-exfoliating techniques have a clearly lower risk of side effects and much less demand for post-operative care. However, the clinical effectiveness of non-peeling methods is often unsatisfactory. The reason for this difference in the clinical outcomes of the two methods is not fully understood. However, one possibility is that damage to the epithelium (or the absence thereof) is an important factor that determines both safe and effective results. The destruction of the outer epithelial barrier (especially the stratum corneum) that plays a role in the apparent exfoliative skin exfoliation increases the chance of wound contamination and the potential for complications. At the same time, the release of growth factors (especially TGF-α) by epithelial cells has been shown to play an important role in the process of wound healing and thus final skin remodeling. Clearly this process does not occur if the epithelium is intact.

  The discovery that the present invention has a substantial advantage when processing tissue using electromagnetic radiation (EMR), resulting in a grid of EMR processed isolated points within the tissue rather than a large continuous region of the EMR processed tissue. It depends in part on. A grid is a periodic pattern of one, two, or three-dimensional isolated points where the isolated points correspond to the maximum points of EMR processing of the tissue. Isolated points are separated from each other by non-processed tissue (or other processed or weakly processed tissue). EMR processing results in a grid of EMR processed isolated points exposed to a specific wavelength or spectrum of EMR, which is referred to herein as an “optical isolated point”. If the absorption of EMR energy results in a significant increase in the temperature of the EMR treated isolated point, the lattice is referred to herein as a “thermal islet” lattice. A lattice is referred to herein as a “damage islet” lattice if a sufficient amount of energy has been absorbed to significantly destroy the cell or intracellular structure. A lattice is referred to herein as a “photochemical islet” lattice when an amount of energy sufficient to initiate a particular photochemical reaction (usually at a particular wavelength) is delivered. By producing EMR-treated isolated points rather than EMR-treated continuous regions, more EMR energy can be delivered to the isolated points without producing thermal or damaged isolated points, and / or Can reduce the risk of major tissue damage.

  Thus, in various aspects, the invention provides improved devices and systems for creating a grid of EMR-treated isolated points in tissue, as well as cosmetic and medical applications to which such devices and systems are improved. .

  In one aspect, the invention provides a method for increasing the permeability of a subject's skin stratum corneum to compounds by creating a grid of EMR-treated isolated points by applying EMR lines to the stratum corneum. In particular, the invention treats the stratum corneum using an EMR processor that creates a lattice of EMR-treated isolated points in the stratum corneum, where the EMR-treated isolated point lattice is sufficient to increase the permeability of the stratum corneum to the compound. Provided is a method for enhancing the permeability of the stratum corneum by heating to a suitable temperature. In some embodiments, the compound is a therapeutic agent such as a hormone, steroid, non-steroidal anti-inflammatory agent, anti-tumor agent, antihistamine or anesthetic. In certain embodiments, the therapeutic agent is insulin, estrogen, prednisolone, lotepredol, ketrac, diclofenac, methotrexate, histamine H1 antagonist, chlorpheniramine, pyrilamine, mepiliramine, emedastine, levocacarbastine or lidocaine. In some embodiments, the compound is a cosmetic agent such as a pigment, a reflective agent, or a photoprotective agent. In general, the lattice of EMR-treated isolated points is heated to a temperature sufficient to at least partially dissolve the crystalline crystalline extracellular matrix without the stratum corneum. In some embodiments, the increase in permeability is irreversible. In some embodiments, the stratum corneum remains damaged until replaced with new growth.

  In another aspect, the invention treats a portion of a subject's stratum corneum with an EMR processor that produces a lattice of EMR-treated isolated points and heats to a temperature sufficient to increase the permeability of the stratum corneum to the compound. Methods are provided for transdermal delivery of a compound to a subject.

  In some embodiments, the invention provides a method for increasing stratum corneum permeability by using an EMR processing device that delivers EMR energy to endogenous chromophores (eg, water, lipids, proteins) in tissue. . In another embodiment, the EMR processing device delivers EMR energy to exogenous EMR absorbing particles that are in contact with the tissue.

  In another aspect, the invention is sufficient to damage tissue within an EMR-treated isolated point, but bulky tissue is subjected to EMR irradiation resulting in an EMR-treated isolated point grid that absorbs an undamaged amount of EMR. Provides a method for selectively damaging a portion of a subject's tissue. In some embodiments, the damage is clotting or denaturation of intracellular or extracellular proteins within the EMR treated isolated point. In another aspect, the damage is cell killing or tissue detachment.

  In another aspect, the invention provides a method for creating a lattice of damaged isolated points in tissue to treat various pathological conditions in the tissue. For example, in some embodiments, a grid of damaged isolated points is created to cause damage to warts, octopuses, psoriasis plaques, sebaceous glands (for acne treatment), sweat glands (body odor treatment), adipose tissue or cellulite tissue.

  In another aspect, the invention treats a portion of the skin with an EMR treatment device that creates EMR treatment isolated points in at least a mass of tissue containing the pigment, thereby preventing the pigment from being killed without killing the cells containing the pigment. A method is provided for reducing pigment in the skin of a subject by destroying. In another aspect, the invention treats a portion of the skin using an EMR treatment device that creates a grid of EMR treatment isolated points in at least a lump of tissue containing the pigment, thereby destroying the cells containing the pigment. Thereby reducing the pigment in the skin of a subject. In any of these embodiments, the pigment may be in a tattoo, port wine nevus, nevus, or buckwheat.

  In another aspect, the invention uses an EMR processing device that activates a natural healing and / or repair process that creates a grid of EMR processing damaged isolated points in a desired treatment area, thereby improving desired tissue properties. Treatment of a portion of the subject's tissue, skin rejuvenation, skin smoothening, removal of thickened scars, wrinkle removal, extension wound removal, smoothing of non-skin surfaces (eg, enlargement of lips), and wounds and Provide a method for improving burn healing.

  In another aspect, the invention processes a portion of a subject's tissue using an EMR processing device that activates a photodynamic agent present in the isolated point by creating a grid of EMR processed isolated points in the desired treatment area. By providing a photodynamic therapy for a subject in need of photodynamic therapy. In some embodiments, the photodynamic agent is administered to the subject prior to treatment. In some embodiments, the photodynamic agent is an antineoplastic agent or psoralen.

  In various embodiments of the invention, the grid of EMR treated isolated points includes a plurality of isolated points, each isolated point having a maximum dimension of 1 μm to 30 μm, 1 μm to 10 μm, μm to 100 μm, 100 μm to 1 mm, 1 mm to 10 mm or more. Can be included. In addition, the lattice may have a fill factor of 0.01-90%, 0.01-0.1%, 0.1% -1%, 1-10%, 10-30%, 30-50%, or higher. Furthermore, the grid of isolated points can have a minimum depth from the tissue surface of 0-4 mm, 0-50 μm, 50-500 μm, or 500 μm-4 mm, as well as a small range that falls within these.

  In various embodiments of the invention, the grid of EMR treated isolated points can be heated to a temperature above 35-40 ° C, 40-50 ° C, 50-100 ° C, 100-200 ° C, or 200 ° C. In some embodiments, the papillary dermis is not heated to temperatures above 40-43 ° C. to prevent pain. In some embodiments, the upper layers of tissue are cooled to reduce heating of these layers and / or create heat below the surface or damage isolated points.

  In another series of aspects, the invention provides an apparatus and system for performing the inventive method.

  In one aspect of the invention, this is an apparatus for performing a treatment on a target area of a patient's skin to create a treatment isolation point. According to this aspect, the apparatus features a housing that defines a target treatment area of the patient's skin when placed near the patient's skin, and an LED or diode laser bar mounted within the housing. An LED or diode laser bar can be used to apply light energy to the target area. LED or diode laser bars include multiple emitters of light energy to create therapeutic isolation points on the patient's skin. The emitters can be separated at various intervals. In one aspect, the emitters are spaced about 50-900 μm apart. The width of the emitter can also be changed. In some aspects, the width is between about 50 μm and 150 μm. In some aspects, the emitter can be in the range of about 50 m to 1000 microns from the patient's skin, and the emitter can create a therapeutic isolation point. The emitter can emit light of various wavelengths included in a wavelength range of about 290 to 10,000 nm, for example. The diode laser bar can include any number of emitters. Some embodiments use 10 to 25 emitters. Another embodiment can incorporate multiple LEDs or diode laser bars in the handpiece to form a stack.

  The apparatus described above can also include various other components such as cooling elements or heating elements attached to the housing. The cooling element can be placed between the diode laser bar and the patient's skin when used to cool the patient's skin. On the other hand, the heating element can warm the patient's skin. In either case, the element can pass at least part of the light energy from the LED or diode laser bar. The cooling or heating element can be made from sapphire or diamond, for example.

  The apparatus can also include a motor for operating the diode laser bar relative to the housing. The device can include a circuit for changing the motor control to move the diode laser bar or LED across the patient's skin in the opposite direction to the movement of the housing.

  The apparatus may include, in some aspects, a mechanism coupled to an emitter for creating a treatment isolation point in the patient's skin. This mechanism may be, for example, a lens array. The mechanism can also be a bundle of optical fibers, where each fiber is connected to at least one emitter.

  The device may be a portable device in some aspects. The portable device may be a portable dermatological instrument including, for example, a control switch and a diode laser bar or button that activates an LED. The portable device may be a stand-alone device or a device that communicates with the base unit via a supply line.

  Another aspect of the invention is an apparatus for treating a target area of a patient's skin by applying light energy to the target area. According to this aspect, the device transmits a light energy source, an applicator that can move near the target area of the patient's skin to apply the light energy to the target area, and transmits light energy from the light energy source to the applicator. Including one or more optical fibers. The applicator can include a mechanism for delivering light energy to the target area to create a process isolation point. The mechanism may be a total reflection element, for example. The light energy source can be either a coherent or incoherent light source.

  Another aspect of the invention is a portable dermatological device. In this aspect, the apparatus includes a plurality of optical fibers residing in a housing in which a head portion of the housing can be placed near the patient's skin by manual operation and a housing for directing radiation from the radiation source through the headpiece to the patient's skin. including. In this aspect, the optical fiber can also output illumination that creates a processing isolation point in a spatially separated state.

  Another aspect of the invention is an apparatus that includes a speed sensor for treating skin. In this aspect, the apparatus features a light emitting assembly for applying light energy to a target area of the patient's skin, said light emitting assembly being from a head portion capable of traversing the target area of the patient's skin and the light energy from the light emitting assembly. Including a light energy source for output. The source is movably attached to the head and a sensor measures a motion measure of the head portion across the target area of the patient's skin. The apparatus controls the movement of the source relative to the head portion based on a motion measure of the head portion across the target area of the patient's skin so as to create a process isolation point on the target area of the patient's skin. A circuit in communication with the sensor can be included. The circuit may, for example, cause the source to move in a direction generally opposite to the direction of movement from the first position of the head portion to the second position of the head portion and generally at the same speed as the movement of the head portion. The source movement can be controlled to return to the first position when the second position is reached. The source can be attached to a linear translator in the head portion, for example. In some aspects, the sensor may be a capacitive imaging array or an optical encoder. The source can be either a coherent or incoherent light source.

According to another aspect of the invention, an apparatus for treating a target area of a patient's skin can prevent light from passing through the patient's skin when the apparatus is not in contact with the patient's skin. . Such an apparatus can feature a light emitting assembly that includes an incoherent light source for applying light energy to a target area, and a plurality of light direction indicating elements at the output end of the light emitting assembly. The light directing element can be formed such that substantially no light passes through the end when the output end does not contact the patient's skin. Furthermore, the light directing element can create a treatment grid on the patient's skin during use. The light directing element can be selected from the group comprising, for example, a pyramid, cone, hemisphere, groove, or prism array.
According to another aspect of the invention, an apparatus for treating a target area of a patient's skin includes an incoherent light source for applying light energy to the target area, and light for spatially modulating output light. A light emitting assembly output end element including a light diffusing surface with a transmissive spot. The light transmissive spot may be one or more of a circle, a slit, a rectangle, an ellipse, or an indeterminate shape.

  Another aspect of the invention is a light emitting assembly for use in treating a target area of a patient's skin. According to this aspect, the light emitting assembly includes an incoherent light source and a light guide for transmitting light energy from the light source to the target area. The light guide may include a bundle of optical fibers that create an isolated point of treatment on the patient's skin during use. The fibers may be present at spaced intervals at the output of the light emitting assembly, for example, to create a process isolation point. Further, a microlens may be attached to the output end of the light guide to focus the light and / or modulate the light. The light source may be, for example, a linear flash lamp, an arc lamp, an incandescent lamp, or a halogen lamp.

  Another aspect of the invention features a light emitting assembly that includes a plurality of incoherent light sources and a plurality of light guides. Each light guide can deliver light energy from one different light source to a target area of the patient's skin. In this aspect, a plurality of light guides provide spatial light modulation. The output end of the light guide can be used to create an isolated point of treatment on the patient's skin. In this aspect, the light source may be a linear flash lamp, an arc lamp, an incandescent lamp or a halogen lamp.

  Another aspect of the invention is an apparatus for treating a target area of a patient's skin, including a light emitting assembly and a mask. The light emitting assembly is for applying light energy from a light energy source to a target area of a patient's skin. The mask is attached to the light emitting assembly, and the mask is positioned between the light energy source and the target area when the apparatus is in use. The mask includes one or more dielectric layers having a plurality of openings for passing light energy from the light energy source through the target area. This allows the device to create a treatment isolation point on the patient's skin. In this aspect, the dielectric layer can have a high reflectivity for the entire spectral band emitted from the light energy source. The openings of the mask may be different in shape or the same. For example, the opening may be a line, a circle, a slit, a rectangle, an ellipse or an indeterminate shape. In some aspects, the apparatus may include a cooling or heating element to cool or warm the mask during use. The light energy may be over a wide wavelength band. In one embodiment, infrared light is used. The light energy can be applied with a pulse width of 100 fsec to 1 second.

  In another aspect, the dermatological device is a housing that can be manually operated to place the head portion of the housing near the human skin, a light path between the energy source and the head portion, and a perforated mirror. Can be included. The mirror is in the light path and the hole allows light energy from the energy source to pass through the target processing area. Such a device can be used to create a treatment isolation point on human skin. The energy source may be in the device or in a separate unit.

  In another aspect of the invention, an apparatus for applying a treatment to a target area of a patient's skin includes a light emitting assembly for applying light energy to the target area and an element attached to the light emitting assembly. The element is disposed between the light emitting assembly and the target area of the patient's skin when the device is used, and the element reflects the light energy from the light emitting assembly back into the light emitting assembly, and the like Including a reflective member opening that allows light energy from the light emitting assembly to pass therethrough.

  According to another aspect of the invention, the apparatus can include a wrinkle removal device or a vacuum source. According to one aspect, such a device features a wrinkle removal device that lifts and stretches the target area of the skin under the wrinkle removal apparatus, and a light emitting assembly for applying light energy to the target area. In use, the light emitting assembly can be oriented to emit light to the patient's skin and treat the patient's skin. The light emitting assembly, in one aspect, can create a treatment isolation point in the patient's skin.

  Another aspect of the invention is a method for applying a treatment to a target area of a patient's skin under a skin wrinkle. According to this aspect, the method lifts the patient's skin to create a skin ridge, and generally the light is applied from the opposite side of the skin so that the light intersects the target area of the patient's skin. including.

  Another aspect of the invention is a composition for use in treating a target area of a patient's skin. The composition features a material that can be selectively applied over a target area portion of the patient's skin. The substance may comprise an absorbable exogenous chromophore. Application of light energy to the material selectively heats the target area portion. In one aspect, the composition can include a high concentration of chromophores such that the treatment creates a treated isolated spot in the patient's skin. The chromophore can be dispersed in the composition such that only the portion of the composition having the chromophore is heated when light energy is applied.

  Another aspect of the invention features a material used to treat a target area of a patient's skin. The material features a film that can be applied over a target area of the patient's skin and a composition that contains an absorbable exogenous chromophore. The composition is selectively added to the film portion such that when light energy acts on the composition, the target area portion adjacent to the composition is selectively heated. The chromophore may be carbon, metal, organic dye, non-organic pigment, or fullerene. In one aspect, the composition can be printed on the patient's skin using a print head. The film may be, for example, an optically transparent polymer.

  Another aspect of the invention is a kit for use in applying treatment to a target area of a patient's skin. The kit may include a material that can be applied over a portion of the target area of the patient's skin and a light emitting assembly for applying light energy to the target area of the patient's skin. The substance may comprise an absorbable exogenous chromophore. In this aspect, when light energy from the light emitting assembly acts on the material, the exogenous chromophore is heated to selectively heat the target area portion of the patient's skin. In one aspect, the light energy has one or more wavelength bands that match the absorption spectrum of the absorbing exogenous chromophore. In some aspects, the substance may be a patch or lotion for application to the patient's skin.

  Another aspect of the invention is a housing that can be manually operated, allows the head portion of the housing to be positioned near the patient's skin, and the head portion can define a target treatment area of the patient's skin when in contact with the patient's skin. A dermatological device characterized by The apparatus also includes a substrate having a plurality of absorbing elements, where incident radiation from the energy source heats the absorbing elements, which creates a processing isolation point in the stratum corneum of the patient's skin. The substrate may be, for example, a mask that blocks incident radiation in a mask area that does not have an absorbent element. The mask may in some embodiments be a contact plate that acts as a cooling plate. The absorbent element can be a variety of materials, such as carbon or metal.

  Another aspect of the invention is a dermatological delivery device. According to this aspect, the device includes a substrate having a plurality of absorbent elements and a composition contained on at least one surface of the substrate. Incident radiation from the energy source heats the absorbent element, which creates a treatment isolated point in the stratum corneum of the patient's skin. After removal of the substrate, at least a substantial portion of the composition remains on the patient's skin.

  Another aspect of the invention is a light emitting assembly for use in treating a target area of a patient's skin. According to this aspect, the assembly comprises a solid state laser, a fiber bundle for receiving light energy from the laser, and a focal point at the fiber bundle output end for projecting light energy from each fiber of the fiber bundle onto the target area. An optical element can be featured. The fiber bundle can spatially modulate the light energy from the laser to create an isolated point of treatment on the patient's skin.

  According to another aspect of the invention, a light radiation assembly for use in treating a target area of a patient's skin is a solid state laser, a phase mask having a plurality of openings for transmitting radiation from the laser And a focusing optical element at the output end of the phase mask and providing spatial modulation of light to the target area. The light emitting assembly can be used to create an isolated point of treatment on the patient's skin.

  Another aspect of the invention includes a light emitting assembly for use in treating a target area of a patient's skin. The optical radiation assembly may include a bundle of fiber lasers and a focusing optical element at the output end of the bundle for focusing the radiation of each laser to a target area. The bundle of fiber lasers and the focusing optical element can create an isolated point of treatment on the patient's skin.

  Another aspect of the invention is an apparatus for treating a target area of a patient's skin that includes a light emitting assembly and a plurality of light directing elements. The light emitting assembly includes a light source for applying light energy to a target area of the patient's skin. A light directing element is disposed at the output end of the light emitting assembly to spatially modulate and concentrate the output light. Light energy can be applied to multiple subregions without affecting a substantial portion of the target region between the remaining subregions. In one embodiment, the light source is selected from a linear flash lamp, an arc lamp, an incandescent lamp, or a halogen lamp. In another embodiment, the light source may be a solid state laser, a fiber laser and a dye laser. In one aspect, the light directing element may be a reflector, a mask, or a light duct. In another aspect, the light directing element may be a microlens or an array of pyramids, cones, hemispheres, grooves, or prisms. In another aspect, the light directing element is a focus optical element at the output end of the fire bundle for projecting light energy from each fiber of the fiber bundle onto the target area.

  The present invention is intended for photodynamic therapy, photobleaching, photobiological adjustment, photobiostimulation, photobiostimulation, thermal stimulation, thermal coagulation, thermal exfoliation or other applications when processing tissue using electromagnetic radiation (EMR) Regardless of whether or not, the organization relies in part on the discovery that there is a substantial advantage within the EMR processing organization that there is a grid of EMR processing isolated points rather than large, continuous regions. EMR treated tissue is useful for such treatment and is suitable for skin tissue, mucosal tissue (eg oral mucosa, gastrointestinal mucosa), ocular tissue (eg retinal tissue), vaginal tissue and glandular tissue (prostate tissue). Any tissue including but not limited to these may be used.

  The grid is a one-, two- or three-dimensional periodic pattern of isolated points, in which the isolated points correspond to the maximum points of tissue EMR processing. Isolated points are separated from each other by untreated tissue (or tissue that has undergone different or lower treatment). EMR processing results in a grid of EMR-processed isolated points exposed to EMR of a particular wavelength or spectrum, and is referred to herein as an “optical isolated point” grid. In the present specification, the lattice is referred to as a “thermal isolated point” lattice when the temperature of the EMR processing isolated point significantly increases due to the absorption of EMR energy. A lattice is referred to herein as a “damaged isolated point” if a sufficient amount of energy has been absorbed to significantly destroy a cell or intracellular structure. If a sufficient amount of energy (usually at a particular wavelength) is delivered to initiate a particular photochemical reaction, the lattice is referred to herein as a “photochemical isolated point” lattice.

  By creating EMR-processed isolated points rather than EMR-processed continuous areas, the unprocessed areas (or areas that have undergone different or lower processing) surrounding the isolated points act as thermal energy sinks and EMR processes Reduce the temperature rise within the isolated point and / or deliver more EMR energy to the isolated point without creating a thermal or damaged isolated point and / or reduce the risk of major tissue damage Can do. Furthermore, in relation to isolated point damage, the wound edge (ie, the interface between the damaged and intact areas) undergoes body regeneration and repair reactions, but the ratio of wound edge to volume is greater. It should be noted that at the smaller isolated lesion points that become higher, the healing of the damaged tissue is more efficient.

  As described in more detail below, the percentage of the volume of tissue that has undergone EMR treatment and that has not yet been treated (or a different or lower treatment) is calculated as follows: optical isolated point is thermal isolated point, damaged isolated point, or photochemical isolated point Decide what will be. This percentage is called “filling rate” and is reduced by increasing the distance between isolated point center points per fixed volume and / or decreasing the volume of isolated points having a fixed center point distance. .

  Because untreated tissue volumes act as heat sinks, these volumes can absorb energy from the treatment volume without becoming heat or damage isolation points themselves. Thus, the relatively low filling rate allows high fluence energy to be delivered to some volumes while preventing the occurrence of large tissue damage. Ultimately, the raw tissue volume acts as a heat sink, so as the filling rate decreases, the probability that the optical isolated point reaches a critical temperature and produces a thermal isolated point or a damaged isolated point (EMR for the isolated point region). Power density and total irradiation dose are constant).

  Ultimately, as described in detail below, the present invention also depends in part on the discovery applications related to EMR and thermal energy absorption, as well as the dissipation characteristics of the tissue. The invention is based, in part, on these discoveries and improved devices and systems for creating a grid of EMR-processed isolated points in tissue and the combination of such devices and systems with endoscope and catheter technology. Providing improved cosmetic and medical applications of these devices and systems in dermatology, dentistry, ophthalmology, gynecology, otolaryngology and internal medicine. Although the inventive devices, systems and methods are described in detail for dermatological applications, they can be used to treat any tissue surface or small surface area capable of delivering EMR.

References and Definitions The patent, scientific and medical publications referred to herein define the knowledge available to those skilled in the art at the time the invention was implemented. The issued US patents, published and pending patent applications, and other references cited herein are hereby incorporated by reference.

  All technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art unless otherwise defined below. References to techniques used herein refer to techniques generally understood in the art, including variations of those techniques or substitution of equivalents, or techniques developed later that will be apparent to those skilled in the art. And In addition, in order to more clearly and concisely describe the subject matter of the invention, the following definitions are provided for specific terms used in the specification and appended claims.

  Numeric range. As used herein, the recitation of numerical ranges for variables means that the invention can be practiced with variables that are equal to any numerical value within that range. Thus, for variables that are discontinuous in nature, the variable must be equal to any integer value within the numerical range, including the end value of the range. Similarly, for variables that are inherently continuous, the variable must be equal to any real number in the numerical range, including the end value of the range. For example, a variable described as having a number between 0 and 2 can take the number 0, 1 or 2 if the variable is inherently an integer, and the variable is inherently continuous. In some cases, 0.0, 0.1, 0.01, 0.001, or other real numbers, where ≧ 0 and ≦ 2, can also be taken. Ultimately, a variable can take on multiple values within a range, including a small range of values within the quoted range.

  Or (or). As used herein, unless stated otherwise, the word “or” is used to include “and / and / or / or” and “either / or / or”. "Is not used for the exclusive meaning.

  Skin structure. While the inventive device and system, and the general method of the invention can be implemented in many tissues of the body, the most common EMR treatment applications currently are in the field of dermatology. Therefore, the structure of the skin, including its constituent tissues, will be described in some detail below, and the rest of the disclosure will use skin as an example. In addition, specific applications that are inherently adapted to the skin (eg tattoo removal, stratum corneum permeation) are also described. However, the general method can be applied to other tissues, and one of ordinary skill in the art can appreciate that the disclosed techniques can be adapted to other organs and tissues with only routine experimentation.

  The skin is the largest organ in the human body and consists of several different tissue layers with different properties, with a thickness of about 0.5 mm to about 4 mm. FIG. 1 depicts a typical cross-sectional view of skin 150, showing various layers with different cells and subcellular structures.

  The skin lies on top of the superficial fascia or subcutaneous tissue 160, which is a layer of adipose tissue covering the denser fibrous fascia.

  Above the subcutaneous tissue is the dermis 170, which contains fibrous elastic connective tissue and has a thickness from about 0.3 mm on the eyelid to about 3.0 mm on the back. The dermis is rich in blood vessels and is organized into small nerve bundles that ascend along the blood vessels and lymphatic vessels, forming a neural network that interlaces under the epithelium, the superficial plexus of the papillary dermis, Includes a variety of sensory nerves with temperature, pressure and pain receptors. Some nerves are thought to penetrate the skin a short distance. The dermis contains two layers: a reticular layer 171 and a nipple layer 172. The reticulated layer 171 contains cells in a matrix of dense, coarse bundles of collagen fibers. The nipple layer 172 contains cells in a matrix of sparse collagen fibers and elastic fibers, with ridges or nipples protruding towards the epithelium.

  The epithelium 180 includes the outermost overlapping layer of the skin, and the thickness ranges from about 0.05 mm of the eyelid to about 1.5 mm of the palm and sole. The epithelium has no blood vessels and consists mainly of epithelial cells.The epithelial cells mature while moving from the innermost cylindrical cell layer to the outermost tile-shaped flat cell, and the cells become flatter toward the outside. Increases thickness and is keratinized. The innermost layer is called the basal layer, basal cell layer, or germ layer 181 and is the only layer in the normal epithelium where cell division occurs. The next layer, spiny layer 182 contains spinous cells and keratinocytes and begins production of keratin. The next layer, the granule layer 183, is a darkened layer with intracellular granules and active keratin production. In thickened skin, there is an additional transitional layer, the faint layer 184. Finally, the outermost layer is the stratum corneum (SC) 185, the stratum corneum of highly keratinized squamous cells.

  The cells of the stratum corneum 185 (and the light layer 184, if present) are highly keratinized (“keratinized”) and are surrounded by an extracellular matrix composed primarily of crystallin lipids. As a result, the stratum corneum forms a hard, resilient barrier to water movement and is impermeable to most aqueous or organic solvents or solutes. The stratum corneum 185 is about 15 μm deep at most anatomical sites, but ranges from 10 to 300 μm (eg, 20 μm at the forearm and 50-60 μm at the wrist).

  Also shown in the skin are common organs and structures, including hair follicles 190, blood vessels 191, nerve fibers 192, sweat glands 193, sebaceous glands 194, and napped muscles 195.

  Normal skin temperature is about 29-37 ° C. When exposed to temperatures above 40-43 ° C., the dermal sensory nerves convey a pain response in most human subjects.

  FIG. 2 is a cross-sectional view of a human skin cross-section 150. The depth of skin from the surface is shown in μm. The stratum corneum 185 and the light layer 184 are drawn extending to a depth of about 15 μm below the skin surface. The remaining layers of epithelium 180 (i.e., layers 181-183) extend from the light / horny layer 184/185 to the boundary with the dermis at a depth of about 50-150 [mu] m from the surface. Exemplary superficial isolated points acting on the clear / horny layer 184/185, deeper isolated points acting on the clear / horny layer 184/185 and deeper epithelial layer 180, and deeper epithelium Also depicted are subsurface isolated points 198 that extend into portion 180 and upper dermis 170.

  The depth shown in FIG. 2 is merely an example. In other parts of the general human body, the stratum corneum / light layer, epithelial and dermal thickness profiles are different. In addition, a variety of other isolated points not shown in the figure are possible, as described below (eg, isolated points of the entire dermis; isolated points of the entire subcutaneous tissue; Isolated isolated points; isolated points extending to epithelium, dermis and subcutaneous tissue sites).

Category of EMR treatment isolated points The present invention relies in part on creating multiple treatment volumes of skin separated by untreated volumes. Volume multiplicity can be described as defining a “grid”, and treated volumes can be described as “isolated points” in the skin because they are separated by untreated volumes. Depending on the nature of the treatment, especially the amount of energy delivered to the isolated point, the degree of tissue heating, or the wavelength of energy, four categories of lattices: optical isolated point (LOI) lattices; thermal isolated point lattices (LTI) ), A lattice of damaged isolated points (LDI), and a lattice of photochemical isolated points (LPCI). These various categories of EMR processing isolated points, devices and systems for creating such EMR processed isolated points, and the cosmetic and medical applications of such devices and systems are discussed separately below. As used herein, the terms “process isolated points”, “process isolated points” and “EMR process isolated points” are used interchangeably and mean any of the categories of isolated points described below.

A. Optical Isolated Points According to the present invention, when a completely or partially separated tissue volume or isolated point is EMR processed, a grid of EMR processed isolated points surrounded by an unprocessed volume is formed. Although isolated points can be processed with any form of EMR, many aspects of the invention use EMRs in the ultraviolet, visible and infrared spectra, so they are conveniently referred to herein as “optical” isolated points. Call. Other forms of EMR useful for the invention include microwave, high frequency, low frequency and direct current induction EMR.

  As described above, when the total transition energy per unit cross-sectional area (ie, fluence), or the energy transfer measure per unit area (ie, flow rate) is sufficiently high, the tissue at the optical isolation point is heated and thermally isolated. Will produce points. If the temperature rise is high enough, the tissue at the thermal isolation point will be damaged, resulting in a damaged isolation point. Thus, although all the thermal isolated points and damaged isolated points are also optical isolated points, not all optical isolated points are thermal isolated points or damaged isolated points. In some embodiments, it may be desirable to create an optical isolated point without creating a thermal or damaged isolated point, as described below. In such an embodiment, the filling rate can be reduced in order to increase the volume of the untreated tissue that acts as a heat sink.

  As described in detail in the examples below, a model of optical isolated points was developed that describes the propagation of light into the skin, taking into account the type of skin and the characteristics of the light source. The specific method used below is applicable to a wide range of isolated point dimensions (eg 10-30,000 μm on the side), is generally accepted for tissue optics, and is called light transport theory (Chandrasekhar ( 1960), Radiative Transfer (University Press, Oxford); Ishimaru (1978), Wave Propagation and Scattering in Random Media, Volume 1 (Academic Press, New York); Jaques et al. (1995), in Optical-Thermal Response of Laser -Irradiated Tissue, Welch et al., Eds. (Plenum Press, New York), pp. 561-606). Briefly, the skin is considered to be a multilayer structure, a turbid medium, where each layer absorbs light and simultaneously scatters light. This method ignores macroscopic interference effects such as diffraction and speckle formation. Several techniques can be used to solve the problem of light transport in the tissue. Some of them, especially 2-flux and diffusion approximations, do not hold when the input beam is thin enough or focused in the tissue, and are unsuitable for dealing with isolated point formation problems. The Monte Carlo method described below has no such limitation, and can model various tissue structures, spot profiles, wavelength spectra, and angular distribution of incident light (Jacques et al. (1995), supra).

B. Thermal Isolation Points According to another aspect of the present invention, EMR processing of isolated volumes or isolated points of tissue can produce a lattice of thermal isolated points that have a higher temperature than the temperature of the surrounding untreated volume. . A thermal isolation point occurs when energy is absorbed significantly faster than it is dissipated by the EMR processing optical isolation point, thereby causing significant heating.

  Heat can be due to water present in the entire volume of the treated tissue, to endogenous chromophores (eg, melanin, hemoglobin) present in selected cells or tissues, or to extraneous chromophores (eg, tattoo smears) within the tissue, or As described below, it can be caused by absorption of EMR by an exogenous chromophore applied to the tissue surface.

For skin, the maximum temperature of the basement membrane near the nerve endings of the papillary dermis should not exceed 40-45 ° C so as not to cause pain to the subject. If the skin surface is not actively cooled, the basement membrane temperature rise, ΔT2, correlates with the temperature rise ΔT1 of the hot isolated point and can be approximated by:
In the formula, f is the filling rate of the optical grating on the skin surface. This formula shows that if the filling rate is sufficiently low, the temperature of the SC can be made relatively high without inducing a body pain response.

  For example, if ΔT2 is 12 ° C. and f is 0.3, ΔT1 is 40 ° C. In fact, the temperature rise ΔT1 may be limited by other factors, such as the structural damage threshold for the SC or the size of the desired damage isolated point.

  The thermal isolated point model is based in part on a time-dependent heat equation. Specifically, as described in detail below, the thermal constant of the skin layer is calculated using the Takata comparison formula (Takata et al. (1977), in Report SAM-TR-77-38 (San Antonio, TX: US Air Force School for Aerospace Medicine)) and is a function of the water volume fraction of the corresponding layer. Specific effects related to the biothermal equation, such as metabolic heat production and changes in blood perfusion measures during live tissue heating, can be ignored for short EMR pulses (Sekins et al. (1990) Thermal Science for Physical Medicine, in Therapeutic Heat and Cold, 4th edition, Lehmann, ed. (Baltimore: Williamis & Wilkins) pp.62-112). In fact, heating by EMR far exceeds the heat of metabolism and heat transport by the bloodstream. Furthermore, changes in blood perfusion measures occur approximately 1 minute later when tissue temperature changes (Sekins et al. (1990), in Therapeutic Heat and Cold, 4th edition, Lehmann, ed. (Baltimore: Williamis & Wilkins) pp.62-112), and the dynamics of isolated point formation as long as the tissue is not simultaneously affected by physical factors (eg high or low external pressure, ultrasound, high or low skin surface temperature) There is no impact.

  It must be emphasized that the lattice of thermal isolated points is a time-dependent phenomenon. If absorption heating is too fast or too long, heat will diffuse from the EMR treatment isolated point and begin to spread into the surrounding untreated tissue volume. When this happens, the thermal isolation points will expand into the raw volume and eventually the thermal isolation points will merge into a large heated body. By using a sufficiently short pulse width for the target temperature relaxation time, fusion or overlap of thermal isolated points in the lattice can be avoided.

C. Damaged isolated points According to another aspect of the present invention, the isolated volume of tissue or EMR treatment of isolated points is surrounded by undamaged (or differently or less damaged tissue) tissue. It is possible to create damaged isolated points. A damaged isolated point occurs when the temperature rise at the EMR treatment temperature isolated point is sufficient to cause protein coagulation, thermal injury, photodisruption, photodetachment, or water evaporation. Depending on the purpose of use, less isolated (eg, protein coagulation, thermal damage) or more damaged (eg, photodisruption, photodetachment, or water evaporation) damage isolated points may be appropriate. As already mentioned, the damage can be caused by water present throughout the treated skin volume, by external chromophores (eg melanin, hemoglobin) present in selected cells or tissues in the skin. It can be caused by absorption of EMR by a sex chromophore (eg, a tattoo smear) or an exogenous chromophore applied to the tissue surface, as described below.

  As described in more detail below, in some embodiments of the invention, the isolated point of damage is thermal damage accompanied by clotting of structural proteins. Such damage can occur, for example, when the light pulse time is changed from a few microseconds to about 1 second, but still keeps the maximum tissue temperature below the evaporation threshold of water in the tissue (Pearce et al. (1995), in Optical-Thermal Response of Laser-Irradiated Tissue, Welch et al., Eds. (Plenum Press, New York), pp. 561-606). The extent of damage is a function of tissue temperature and heat pulse time and can be quantified by several damage functions known in the art. In the following description, for example, the damage function according to the Arrhenius damage integral (Pearce et al. (1995), in Optical-Thermal Response of Laser-Irradiated Tissue, Welch et al., Eds. (Plenum Press, New York) , pp.561-606; Henriques (1947), Arch. Pathol. 43: 480-502). Other mechanisms and models for the formation of damaged isolated points can be applied to embodiments using relatively short and intense pulses, particularly those associated with photodisruption, photodetachment and water evaporation.

D. Photochemical isolated points According to another aspect of the present invention, the isolated volume of tissue or EMR treatment of isolated points can create a lattice of photochemical isolated points surrounded by a tissue volume in which no photochemical reaction was induced. it can. The photochemical reaction can include an endogenous biomolecule or an exogenous molecule. For example, exposure of skin to certain wavelengths of EMR can cause increased production of melanin and “sunburn” through activation of endogenous biomolecules and biological pathways. Or, for example, exogenous molecules can be administered as a photodynamic therapy, and activation of these molecules by a specific wavelength of EMR can produce a systemic or local therapeutic effect.

Treatment Parameters In the practice of the invention, various types of treatment parameters related to the EMR to be acted upon can be controlled and varied according to specific cosmetic and medical applications. These parameters include, but are not limited to, the following:

A. Shape of EMR treated isolated point The optical isolated point can be made in any shape that can be created by the apparatus described below as long as the EMR beam in the tissue can be controlled. Thus wavelength, time characteristics (eg continuous vs. pulse delivery), and EMR fluence; EMR beam profile, incidence angle and focus; and tissue layer refractive index, absorption coefficient, scattering coefficient, anisotropy factor (scattering angle Depending on the average cosine) and structure; and the presence or absence of exogenous chromophores and other substances, the isolated points may extend from the skin surface through one or more layers, or from just below the skin surface through one or more layers, or A volume having various shapes such as existing in a single layer. When the beam is non-convergent, the beam defines a volume having a substantially constant cross-sectional area in the plane orthogonal to the optical axis (eg, cylindrical, rectangular). Alternatively, the beam may be convergent, defining a volume with a gradually decreasing cross-sectional area in a plane orthogonal to the beam center axis (eg, cone, triangular pyramid). The cross-sectional area may be in a regular form (eg, ellipse, polygon) or any form. In addition, depending on the wavelength and fluence of the EMR beam and the absorption and scattering properties of the tissue for that wavelength, the EMR beam penetrates to a certain depth before it is first or fully absorbed or dissipated, The EMR treatment isolated point will not span the full width of the skin, but rather will span between the surface and a specific depth, or two depths below the surface.

  In general, a lattice is a periodic structure of one, two or three-dimensional isolated points. For example, a two-dimensional (2D) lattice is periodic in two dimensions, but invariant or non-periodic in three dimensions. The periodicity type is characterized by a voxel type. For example, but not limited to these, layered, four-sided, hexagonal or rectangular lattices are conceivable. The number of dimensions of the grid may be different from the individual isolated points. A single row of equally spaced infinite cylinders is an example of a 1D grid of 2D isolated points (if the cylinder has a finite length, this is a 1D grid of 3D isolated points). The number of dimensions of the grid is less than or equal to the dimension of the isolated point (this fact comes from the fact that the grid cannot be periodic in the dimension where the isolated point is transition invariant). Thus, there are a total of six types of grids, each type being an allowed combination of isolated points and grid dimensionality. For some applications, use an “inverted” lattice in which the isolated points of intact tissue are separated by an EMR-treated tissue region and the treatment region is a collection of consecutive treated tissues with untreated isolation regions. Can do.

  Referring to FIG. 3A, each processing volume may be a relatively thin disk as illustrated, a relatively elongated cylinder (eg, extending from a first depth to a second depth), or substantially its width and depth. May be a volume that is substantially linear and that is oriented substantially parallel to the surface of the skin. In the illustrated application, the line directions of the isolated points 214 may not all be the same, and some lines may be perpendicular to other lines, for example (see, eg, FIGS. 4A and 4B). The line can also be directed around the processing target for greater efficiency. For example, the line may be perpendicular to the blood vessel or parallel to the wrinkles. The isolated point 214 may be a subcutaneous volume shaped like a sphere, ellipse, cube, or cuboid with a selected thickness. The isolated point may also be a substantially straight or planar volume. The shape of the isolated point is determined by a combination of beam optical parameters, including beam size, amplification and phase distribution, application time, and to a lesser extent the wavelength.

  The parameters for obtaining the shape of a specific isolated point can be determined empirically only from ordinary experiments. For example, a low conversion beam 1720 nm laser operating at a pulse width of about 0.005 to 2 Joules and 0.5 to 2 ms can create a generally cylindrical isolated point. Alternatively, a 1200 nm laser with a high conversion beam of about 0.5-10 joules and a pulse width of 0.5-3 seconds can generally create an elliptical isolated point.

  Regardless of shape, the isolated point can be spread over the entire volume, made into a bulky thin single layer, or adjacent isolated points, with appropriate control of wavelength, focusing, surface incident beam and other parameters Can be shifted so that is present in another bulky thin layer. Most structures in the grid of isolated points can be formed sequentially or simultaneously. A grid of isolated points within a plurality of thin layers in a volume can be easily and continuously shaped using, for example, a scanner or using a plurality of energy sources having different wavelengths. Isolated points of the same or different depth can be created, and isolated points at various depths when viewed from the skin surface can be spatially separated or overlapped.

  The geometry of the isolated points affects the thermal damage of the processing area. Since the sphere has the greatest gradient and therefore the smallest spatiality, it will cause the most localized biological damage and therefore may be preferred for applications where local damage is desirable.

B. Size of EMR-processed isolated points The size of individual isolated points within the grid of EMR-processed isolated points of the invention is highly dependent on the intended cosmetic or medical application. As discussed in more detail below, in some embodiments, it is desirable to cause substantial damage and destroy tissue structures or regions (eg, sebaceous glands, hair follicles, tattooed parts), but in other embodiments, certain It is desirable to do little or no damage while applying an effective amount of wavelength EMR (eg, photodynamic therapy). However, as discussed above with respect to isolated point damage, healing of damaged tissue is more effective with smaller damaged isolated points, where the ratio of wound edge to volume is greater.

  In general, the size of the EMR treated isolated point of the present invention can vary from 1 μm to 30 mm for any particular dimension. For example, a grid of isolated points that are substantially straight may comprise parallel isolated points that are about 30 mm long and about 10 μm to 1 mm wide, but are not limited to these. As another example, for an isolated point where the axis of the cylinder is substantially a cylinder perpendicular to the tissue surface, the depth may be about 10 μm to 4 mm and the diameter may be about 10 μm to 1 mm, It is not limited to these. For a substantially spherical or elliptical isolated point, the diameter or principal axis may be, for example, but not limited to about 10 μm to 1 mm. Thus, in some embodiments, the isolated point takes the largest dimension in all possible ranges falling from 1 μm to 10 μm, 10 μm to 100 μm, 100 μm to 1 mm, 1 mm to 10 mm, or 10 mm to 30 mm, and 1 μm to 30 m. Can do.

When considering the size of optical, thermal, damage or photochemical isolated points of the invention, the boundaries of isolated points may not be clearly demarcated, or rather very continuous or untreated tissue (or processed) It is important to note that they may be mixed with different or lesser organizations. For example, since the EMR beam is scattered by various tissues, even a beam of interfering light will diffuse if it passes through multiple layers of cells or tissues. As a result, optical and photochemical isolation points generally do not have a clear boundary between the treated and untreated volumes. Similarly, thermal isolated points generally exhibit a temperature gradient from the center of the isolated point toward its boundary, and the untreated tissue surrounding the isolated point will also exhibit a temperature gradient due to heat conduction. Finally, the isolated point of damage may have an indefinite or obscure border due to partially damaged cells or structures or partially coagulated proteins. Therefore, as used herein, the size of an isolated point within an isolated point grid refers to the size of the isolated point defined by the intended minimum or threshold amount of delivered EMR energy. As discussed in more detail below, this amount is expressed as the minimum fluence, F _min , and is determined by the nature of the cosmetic or medical application. For example, in photodynamic therapy, F _min is determined by the minimum fluence required to cause the desired photochemical reaction. Similarly, when increasing the permeability of the stratum corneum, F _min can be determined by the minimum fluence required to achieve the desired SC temperature, and when disrupting tissue, F _min can exfoliate tissue. Or the minimum fluence required to evaporate the water. In each example, the size of the EMR process isolation point is defined by the size of the tissue volume that receives the desired minimum fluence.

  Due to the scattering effect of the tissue, the minimum size of the EMR treated isolated point increases with the target depth in the tissue, ranging from a few microns for the stratum corneum to a few millimeters for the subcutaneous tissue. At a depth of about 1 mm of the subject's tissue, the minimum diameter or width of the isolated point is about 100 μm, although larger isolated points (eg, 1-10 mm) are possible. The size of the damaged isolated point may be smaller or larger than the size of the corresponding optical isolated point, but generally it is larger because more EMR energy is added to the optical isolated point for thermal diffusion reasons. Become. For the smallest isolated point at any depth in the skin, the wavelength, beam size, focus, energy and pulse width must be optimized.

C. Depth of EMR-processed isolated points Inventive EMR-processed isolated points are located at various points in the tissue, including surface and subsurface positions, relatively limited depth positions, and positions that extend to substantial depths. Can be placed. The desired depth of the isolation point depends on the intended cosmetic or medical application, including the targeted molecule, cell, tissue or intracellular structure.

  For example, the optical isolation point can lead to various depths of tissue or organs depending on the penetration depth of EMR energy, which depends in part on wavelength and beam size. Thus, an isolated point may be a superficial isolated point that exists only in a tissue surface layer (for example, 0 to 50 μm), a deep isolated point that exists over a plurality of tissue layers (for example, 50 to 500 μm), or an extremely deep subsurface isolated point ( For example, 500 μm to 4 mm). When light energy is used, a maximum depth of 25 mm can be reached using a wavelength of 1,000 to 1,300 nm. When using microwave and high frequency EMR, it can reach a depth of several centimeters.

  In the case of thermal or damaged isolated points, subsurface isolated points can be created by targeting chromophores that are present only at the desired depth, or by cooling the upper layer of tissue during delivery of EMR. Long pulse widths combined with surface cooling are particularly effective when creating deep heat or damaged isolated points.

D. Filling rate of EMR processing grid
In any grid of EMR-treated isolated points, the percentage of tissue volume that has undergone EMR treatment is called the “fill factor” or f, which affects whether the optical isolated point becomes a thermal, damaged or photochemical isolated point To do. The fill factor is defined by the volume of isolated points relative to a reference volume that contains all isolated points. The filling rate may be uniform for a periodic grid of isolated points within the EMR process isolation point having a uniform size, or may vary throughout the process area. It can be created in situations that include, but are not limited to, the creation of thermal isolation points by locally applying EMR absorbing particles as a lotion or suspension (see below). For this situation, the average filling factor (f _avg) is dividing the volume V _i ^{islet I} of all EMR treatment isolated points in all tissue volume V _i ^tissue processing region
Can be calculated.

In general, the filling factor can be lowered by increasing the center-to-center distance of a fixed volume of isolated points. Thus, the filling rate calculation will depend not only on the volume of the EMR processing isolated points, but also on the spacing between the isolated points. For periodic grids where the distance between the centers of the nearest isolated points is d, the filling factor will depend on the ratio of the size of the isolated points to the distance d between the nearest isolated points. For example, for a grid of cylindrical isolated points in parallel, the filling factor would be:
In the equation, d is the shortest distance between the centers of the nearest isolated points, and r is the radius of the cylindrical EMR processing isolated point. For a grid of spherical isolated points, the fill factor will be the ratio of the volume of the spherical isolated point to the volume of the cube defined by the adjacent centers of the isolated points:
In the equation, d is the shortest distance between the centers of the nearest isolated points, and r is the radius of the spherical EMR processing isolated point. Similar formulas are obtained for calculating the fill factor of a grid of isolated points with various shapes such as lines, disks, ellipses, cuboids or other shapes.

  Since the volumes of untreated tissue act as heat sinks, these volumes can absorb energy from the treatment volume without itself becoming a heat or damage isolation point. Thus, the relatively low filling rate can deliver high fluence energy to several volumes while preventing significant tissue damage. Eventually, the volume of untreated tissue acts as a heat sink, which reduces the filling rate and at the same time reduces the probability that the optical isolated point will reach a critical temperature and produce a thermal isolated point or a damaged isolated point (EMR power for the isolated point region). Even if density and total exposure remain constant).

  The distance between the centers of isolated points depends on a number of factors including the size of the isolated points and the processing performed. In general, the distance between adjacent isolated points must be sufficient to protect the tissue and promote healing of the added damage while at the same time achieving the desired therapeutic effect. Generally, the filling rate is in the range of 0.1 to 90%, and in other applications it is in the range of 0.1 to 1%, 1 to 10%, 10 to 30% and 30 to 50%. The interaction between the filling rate of the EMR processing isolated points and the thermal decay time will be described in detail below. In the example of a grid of thermal isolated points, it is important that the filling rate is sufficiently small so that the isolated points are not overheated and damaged, whereas in the example of a grid of damaged isolated points, around each damaged isolated point It is important that there is enough undamaged tissue to prevent significant tissue damage and is small enough to allow the damaged volume to heal.

Application of EMR processing isolated points
EMR treated isolated points can be used for a variety of applications in different types of organs and tissues. For example, EMR treatment includes, but is not limited to, skin, mucosal tissue (eg, oral mucosa, gastrointestinal mucosa), ocular tissue (eg, conjunctiva, cornea, retina) and glandular tissue (eg, lacrimal sac, prostate). Can be applied to organizations that do not. As a general matter, methods include injury (eg, sores, ulcers), acne, red nose, wasted hair, unwanted blood vessels, hyperplastic growth (eg, tumors, polyps, benign prostatic hyperplasia), hypertrophic growth (eg, benign prostatic hyperplasia). , Including angiogenesis (eg, neovascularization related to tumors), dysplasia of arteries or veins (eg, blood vessel type, flaming nevus), and unwanted pigmentation (eg, pigmented nevus, tattoos), but these It can be used for the treatment of conditions not limited to the above.

A. Thermal Isolation Point In some aspects, the invention provides a method of treating tissue by creating a grid of thermal isolation points. These methods can be used in methods for increasing the permeability of the stratum corneum to various agents including, for example, therapeutic agents and cosmetics, as well as methods for creating therapeutic hyperthermia.

1. Reversible permeability of stratum corneum In one embodiment, a lattice of thermal isolated points is created to reversibly increase the permeability of the stratum corneum by heating the isolated points of the tissue to a temperature of 35-100 degrees. It is done. Increased permeability occurs by lysing the extracellular matrix of crystalline lipids surrounding the stratum corneum and, if present, the cells of the light layer. As the matrix dissolves (ie, its crystal structure relaxes), the SC becomes more permeable to molecules on the skin surface and some molecules can diffuse inside. When the layer temperature is returned to normal (ie 29-37 ° C), the intracellular matrix crystallizes, the SC becomes more impervious, molecules that have already diffused under the SC remain there, and further diffuse into the surrounding tissue. Or enter the systemic bloodstream. Thus, as used herein, the increased permeability is “reversible” because the lipidic intracellular matrix recrystallizes. In another embodiment, the increased permeability returns between 1 second and 2 hours after discontinuing EMR treatment. Thus, in some embodiments, the increase in permeability returns within 15 minutes, 30 minutes, 1 hour, or 2 hours after discontinuing EMR treatment.

  In these embodiments, the thermal isolation point defines a permeation path that can spread through, or mostly through, the stratum corneum and the light layer, and compounds used on the outer surface of the skin, such as cosmetics or therapeutic agents, are effective. It can penetrate into the stratum corneum / light layer. This penetration may be superficial and may remain directly below or within the stratum corneum, or may penetrate deeper into the inner layer of the epithelium or dermis and enter the bloodstream via blood vessels in the dermis. I may be able to do it. This allows cosmetic or therapeutic agents to be delivered topically to the skin or dermis transdermally. If the compound diffuses from the treatment site, local delivery of the compound can be extended (eg, delivery to the joint area). Furthermore, if the compound can reach the dermal blood vessels, delivery will be systemic.

  In some embodiments, the compound is a therapeutic agent. Examples of therapeutic agents include, but are not limited to, hormones, steroids, non-steroidal anti-inflammatory drugs, anticancer drugs, antihistamines and anesthetics. Specific examples include hormones such as insulin and estrogen, steroids such as prednisolone and loteprednol, nonsteroidal anti-inflammatory drugs such as ketolac and diclofenac, anticancer agents such as methotrexate, and histamine H1 antagonists, chlorpheniramine Antihistamines such as, but not limited to, pyrilamine, mepyramine, emedastine, levocabastine and lidocaine.

  In another aspect, the compound is a cosmetic product. Examples of cosmetics include pigments (including natural and synthetic chromophores, dyes, colorants or inks), reflective agents (including light scattering compounds) and photoprotectors (including sunscreens), It is not limited. Such cosmetics can be used to color the skin by adding pigments or reflectors of different colors, or to mask existing colors (eg, maternal, pigmentation disorders, tattoos). The invention includes (a) that the agent is contained within the stratum corneum and that it is not applied, rubbed or washed away, and (b) that the agent has normal growth from the basal layer. It remains within the stratum corneum until it is replaced throughout the process (eg, approximately 21-28 days), thus providing an improved cosmetic application. Thus, the use of a single cosmetic product may last for several weeks, which is advantageous over cosmetic products that must be used daily. Conversely, cosmetic applications are limited to a few weeks, which is an advantage over tattoos that usually last until they are removed by photobleaching or tissue peeling. In one embodiment, the pigment can be applied to the skin for the desired temporary tattoo (eg, by film, brush, printing) and the stratum corneum can be EMR treated to increase permeability, and the pigment is contained in the skin. It can diffuse to make temporary tattoos. In another aspect, an artificial tan can be created by delivering a colorant, or conversely, a sunscreen can be prevented by delivering a sunscreen into the skin.

  Increased permeability of the stratum corneum can be made painless or less painful to the subject by using a grid of thermal isolated points (or damaged isolated points) rather than a continuous heated region. Since the entire skin and width are not heated, the 40-43 ° C. isotherm can be kept near the epithelium / dermis boundary rather than deeper in the dermis. Thus, nerve endings in the nipple dermis are not exposed to temperatures of 40-43 ° C and are not accompanied by pain reactions. As a result, the hyperpermeability pathway defined by the thermal isolation point can be made without exposing the SC to temperatures significantly higher than 40-43 ° C.

  When the temperature of the extracellular lipid of SC rises to the transition temperature Tm where the lipid state changes from an intermediate (lipid crystal) state to a liquid state (Tm = 64 ° C in rat SC, Ogiso et al. (1996), Biochem. Biophys Acta 1301 (102): 97-104), a large increase in the permeability of the stratum corneum (order scale) occurs. A simple estimate of the heat flux required to reach this temperature and thereby irreversibly dissolve the stratum corneum lipid layer can be obtained as follows.

For example, to perform this calculation, the thickness of the SC can be set to d = 15 μm that can be found on the palmar forearm. The stratum corneum (SC) has been found to be a mixture of water, lipids and proteins in approximately the following weight ratios: W1 = 20% water, W2 = 50% lipids and W3 = 30% protein. SC lipids are made up of: ceramide (50%), cholesterol (28%), free fatty acids (17%) and cholesterol sulfate (5%). The thermal parameter of the SC is determined and is the total load of the corresponding parameter of the component, loaded with the appropriate weight factors W1, W2 and W3:

A typical initial SC temperature is T ₀ = 30C. The SC latent heat of fusion, λ, (for dissolution) is assumed to be close to the known value for the lipid DPPC (dipalmitoylphosphatidylcholine). This parameter is λ = 14500 J / mol = 2 J / gm, and the molecular weight is 734 gm / mole at this time. Assuming an adiabatic state (ignoring heat loss) and a thermal equilibrium between components, the threshold fluence for dissolving lipid, F, is estimated as follows:

Using the parameter estimates above, the fluence value required to dissolve SC lipids is Fm = 0.07 J / cm ² . This fluence can be achieved in various ways as described herein. For example, EMR may be absorbed directly or converted to heat by one or more components that act as the SC's intrinsic chromophore, or EMR may be due to an exogenous chromophore (such as carbon dots) on the skin surface. May be absorbed. Note that the relative contribution of the energy that actually dissolves the lipid is small (~ 3%) and most of the energy is required to raise the SC from the ambient temperature T ₀ to the melting point T _m .
The thermal decay time TRT of SC is estimated as follows:
For example, a heat flux of ˜1 kWcm ⁻² for 70 μs will satisfy this condition. If the melting temperature must be maintained above the TRT, the required heat flux must be balanced with heat loss after reaching the required temperature.

  The size of the permeabilization pathway ranges from the diameter of the intracellular lipid space (eg 1 μm) or the thickness of the corneocytes (eg 0.5 μm) to approximately the thickness of the SC (eg 10 to 500 μm). However, the permeability pathway is about 20 μm to 1 mm in diameter and less than 50 μm in depth to avoid damage to the live epithelial layer and to reduce or eliminate pain and discomfort. Still, for some embodiments, the thermal isolation point extends into the deeper layers of the epithelium and dermis to desorb them and stimulate blood microcirculation in order to more rapidly absorb the drug into the body Can do. However, when targeting deeper tissues at higher temperatures, patient pain management may be required.

  In general, the thermal isolation point spacing should be as close as possible to maximize permeability and thereby maximize delivery efficiency. However, too dense paths can have a detrimental effect on depth-temperature selectivity. For example, if the spacing is zero, the heat is diffused efficiently only downward, not radially, sufficiently heating the stratum corneum to create a hyperpermeability pathway while simultaneously causing deeper epithelial and dermal damage and pain It becomes difficult to prevent. In general, this does not preclude the use of higher or lower fill rates for this application, but the fill rate is less than 30% but greater than 1%.

2. Thermal Isolation Point of Deep Tissue According to the present invention, and as described in more detail below, creating a thermal isolation point that extends from the tissue surface to a deeper layer of tissue or exists throughout the subsurface layer. (See, for example, FIG. 2, isolated point 198). Such a heat isolated point can be used for applications such as heat-enhanced light biomodulation, photobiostimulation and photobiosuppression, and the creation of damaged isolated points as described below.

C. Damage Isolated Points In some aspects, the invention provides a method of treating tissue by creating a grid of damaged isolated points. These methods include, among others, skin rejuvenation, tattoo removal (eg, killing cells containing black ink particles, peeling of black ink particles), acne treatment (eg, damage or destruction of sebaceous glands, bacterial killing, inflammation) ), Pigmentation injury treatment, vascular injury treatment, and flame-like nevus (“port wine nevus” removal (eg, reducing abnormal blood vessels). It can also be used to increase the permeability of the stratum corneum, and the time taken to recover or heal such damage can be controlled by changing the size of the damaged isolated points and the packing rate of the lattice.

1. Tissue Remodeling In one aspect, the invention provides a tissue remodeling method based on controlled tissue damage.

  One aspect of tissue remodeling is: (a) reduction of abnormal skin discoloration (ie, non-uniform pigment), (b) reduction of telangiectasia (ie, angiogenesis abnormality), (c) improvement of skin texture, And (d) skin “rejuvenation”, a complex process involving one or more of skin tension improvements (eg, increased elasticity, lifting, tension). Techniques used for skin rejuvenation can be broadly classified into three categories: exfoliation techniques, non-exfoliation techniques, and fractionation techniques (including the isolated point grid of the present invention).

In the exfoliation method by exfoliation, the entire width of the epithelium and the upper dermis are exfoliated and / or coagulated at the same time. Exfoliation techniques generally provide more pronounced clinical results, but involve more post-operative recovery time and risk of care, pain and infection. Dermabrasion surgery: In (CO ₂ laser, for example the absorption coefficient ～900Cm ^-1 or from the absorption coefficient, the 3,000 cm ^-1 Er those with YAG laser), requires several weeks recovery period, between the next few months Erythema remains on the treated skin.

In the non-peeling method, the coagulation region moves deeper into the tissue and the epithelium remains intact (eg, using a laser with an absorption coefficient of 5-25 cm ⁻¹ ). Non-exfoliating techniques greatly reduce recovery time and care, pain, and infection risk required after surgery.

  The fractional method is also non-peeling but requires partial or fractional injury to the treatment area instead of coagulating the entire treatment area or injury area. That is, a grid of damaged isolated points is created in the processing area.

  The present invention provides a method for insensitive skin rejuvenation where the heat and damage isolated points are relatively deep within the dermis and subcutaneous tissue (eg, depth> 500 μm from the skin surface). Active or passive cooling of the epithelium can be used to prevent epithelial damage.

2. Lifting and pulling the skin The creation of a lattice of damaged isolated points is the result of the collagen fibers exposed to high temperatures contracting (immediate effect) or (b) lifting the skin as a result of local coagulation in the dermis or subcutaneous tissue, Or you can pull (immediate to short term effect).

3. Smoothing the texture of the skin The creation of a grid of damaged isolated points can smooth the texture of the skin (immediate to short-term effects) as a result of coagulating the dermis and local areas in the subcutaneous tissue. This technique can also be used on textured tissues or organs other than dermis / epithelium (eg, lip enlargement).

4. Promotion of collagen production The creation of a lattice of damaged isolated points can result in the promotion of collagen production as a result of tissue healing response to heat stress or heat shock (medium to long term effect).

5. Tattoo Removal The creation of a grid of damaged isolated points can be used to remove a tattoo by killing the cells containing the tattoo's ink particles (typically the cells of the upper dermis). After killing these cells, the tattoo ink is removed from the tissue site by a normal elimination process. Alternatively or in addition, the lattice of damaged isolated sites can also be used to remove tattoos by selecting the EMR treatment wavelength and allowing the tattoo ink particles to selectively absorb EMR energy. it can. In some embodiments, the pulse width of the incident pulse is chosen to match the thermal decay time of the black particles. Absorption of EMR energy by tattooed black ink particles can heat and kill cells; black ink particles can be photobleached or destroyed into smaller molecules that are removed by normal processes; or another method Can destroy the ink.

6. Increased permeability of stratum corneum The creation of a lattice of damaged isolated points can be used to heat tissue isolated points to temperatures above 100 ° C to drill small holes in the SC. Thus, in such an embodiment, EMR treatment coagulates, detaches, evaporates, or otherwise damages or removes a portion of the SC containing crystallized intracellular lipid structures or cells, creating a lattice of damaged isolated points throughout the SC. . This method provides SC permeability for a longer period of time than the thermal isolation point method described above, because the damaged area or pore remains in the SC until the cell layer is replaced through a normal growth process from the basal layer. Increase (eg about 21-28 days).

7. Acne Treatment The creation of a grid of damaged isolated points targets the sebaceous gland by selecting the wavelength of EMR treatment, causing selective absorption of EMR energy by sebum, or selectively damaging or destroying the sebaceous gland Can be used to treat acne by creating a grid as EMR treatment can also target bacteria within acne ulcers.

8. Treatment of hypertrophic scars The creation of a grid of injured isolated points can be used to treat hypertrophic scars by inducing contraction and adhesion of scar tissue and replacing abnormal connective tissue with normal connective tissue. it can.

9. Reduction of body odor The creation of a grid of damaged isolated points can be used to treat body odor by selectively targeting the eccrine gland, thereby reducing the production of eccrine sweat or altering its composition. .

10. Removal of warts and octopus The creation of a grid of damaged isolated points can be used to treat warts and octopus by selectively targeting the diseased tissue to kill cells or detach the tissue .

11. Psoriasis treatment The creation of a grid of damaged isolated points can be used to treat psoriasis by selectively targeting psoriatic plaques using appropriate wavelength EMR, thereby stopping or reversing plaque formation. it can. The diseased tissue can be replaced with normal tissue by normal biological processes.

12. Wound improvement and burn healing The creation of a grid of damaged isolated points is the time required to heal wounds or burns (including frostbite) by increasing the outer edge of the wound or burn without substantially increasing the volume. Can be used to shorten

13. Cellulite or fat volume reduction The creation of a grid of damaged isolated points can be used to reduce cellulite by changing the distribution of mechanical stress at the dermis / subcutaneous tissue boundary. Alternatively, a grid of damaged isolated points can be used to reduce fat in the subcutaneous tissue (subcutaneous tissue) by heating and damaging the fat cells in the isolated points.

14. Reduction of hair The creation of a grid of damaged isolated points can be used to reduce the amount or presence of body hair by targeting the hair follicle of the skin with the grid of damaged isolated points. The method can selectively target melanin or other chromophores present in the hair or hair follicle, or may non-target water in the hair follicle.

15. Endothelial detachment or fusion The creation of a grid of damaged isolated points can be used to treat conditions such as benign prostatic hypertrophy or hyperplasia or restenosis by damaging or destroying the endothelium. The method can also be used to fuse tissues together by creating damaged areas at the tissue interface.

16. Creating Identification Patterns The creation of a grid of damaged isolated points can be used to create an identification pattern in the tissue that results from tissue or other structure detachment or that results from a tissue healing process. For example, a pattern can be created on the hair shaft by “etching” the hair with a grid of damaged isolated points. Alternatively, the dermis, epithelium or other epithelial tissue can be patterned by using a healing process that creates demarcated areas with different appearances.

D. Photochemical isolated points In some aspects, the invention provides a method of treating tissue by creating a lattice of photochemical isolated points. These methods can be used, for example, to activate EMR-dependent biological responses (eg, melanin production or “sunburn”), and photodynamic treatment (eg, vitiligo or hypopigmentation). For example, vitiligo, white extension wounds (ie, white lines) and hypopigmentation can be treated by creating photochemical isolated points that increase pigmentation in the treated area with or without photodynamic agents. Specifically, melanocyte proliferation and differentiation can be promoted by targeting the basal layer.

Product and Method for Creating a Grid of EMR Processed Isolated Points FIG. 5 is a schematic diagram of an apparatus 100 for creating processed isolated points on a patient's skin that can be used in one embodiment of the invention. In this device 230, light energy 232 from a suitable energy source 234 passes through the optical device 236, filter 238, cooling mechanisms 240, 242 and cooling or heating plate 244 to the tissue 246 (ie, the subject's skin). Each of these components is described in detail below. In general, however, the EMR from the energy source 234 is focused by the optical device 236 and shaped by a mask, optics, or other element to create an isolated point of treatment on the subject's skin. In some aspects of the invention, some of these components may not necessarily be present, such as filter 328 using a monochromatic energy source, or optics 236, for example. In another aspect, the device may not touch the skin. In yet another embodiment, the cooling mechanism 4 is not present and only passively cools between the contact plate and the skin.

  Appropriate optical impedances, typically matching lotions or other compatible materials, are used between the plate 244 and the tissue 246 to enhance optical and thermal coupling. As shown in FIG. 5, the tissue 246 is divided into an upper region 248 that is the epithelium and dermis in an application where electromagnetic radiation is applied to the skin, and a lower region 250 that is the dermis region in the above example. The region 250 is, for example, a subcutaneous tissue.

  FIG. 6 shows a handheld device 260 that may include components of the device 230 described in conjunction with FIG. In particular, the housing 264 of the handheld device 260 may include an energy source 264, an optical device 236, a filter 238, and a cooling mechanism 240 and a cooling plate 244 (only the cooling plate 244 is shown in FIG. 6). In use, light energy passes through the cooling plate 244 and contacts the patient's skin. In some aspects, the housing 264 also includes a button that activates the energy source.

  The handheld device 260 of FIG. 6 also includes a supply or cable connection 266 that connects to a control or base unit that can communicate with the handheld device 260 through control signals. The control unit may include supply of coolant for the cooling mechanism 244, for example. In another aspect, the control unit can include power settings for the energy source (not shown in FIG. 6), etc. in the morphological device 260. In addition, the control unit can include a microprocessor and a control device that control certain features of the invention, as described in detail below. The cable connecting the control unit and the connection 266 of the handheld device 260 may include a supply line for coolant and a wire for control and power supply of the handheld device 260. In another aspect, the energy source may be housed in a base unit and energy is sent through the supply line to the handheld device. For example, light energy can be sent through an optical fiber in a supply line. In another aspect, all components may be housed in a handheld device and the base unit may be eliminated.

  3A and 3B show a schematic diagram of another example system 208 for creating an isolated point of treatment. 3A and 3B show a system for delivering light radiation to a processing volume V located at a depth d of the patient's skin. 3A and 3B also show a treatment or target site 214 (ie, a treatment isolation point) within the patient skin 200. FIG. A portion 200 of patient skin is shown, which includes an epithelium 202 covering the dermis 204, an epithelial-dermis junction called a dermis-epithelium (DE) junction 206. The treatment volume is at the patient skin surface (ie, d = 0) and the treatment isolated point is formed in the stratum corneum. In addition, the treatment volume V may be in one or more treatment layers below the skin surface, or the treatment volume may extend from the skin surface through one or more skin layers.

  The system 208 of FIGS. 3A and 3B can be incorporated into a handheld device, such as the device 260 depicted in FIG. System 208 includes an energy source 210 that produces electromagnetic radiation (EMR). The output from the energy source 210 is sent to an optical system 212 which is preferably in the form of a delivery head that contacts the patient's skin surface as shown in FIG. 3B. The delivery head may include a contact plate or cooling element 216 that contacts the patient's skin, for example (number 244) as also shown in FIG. The system 208 can also include a detector 216 and a controller 218. The detector can, for example, detect contact with the skin and / or a motion measure of the device on the patient's skin, and can image the patient's skin, for example. The controller 218 can be used to control pulsing of the EMR source in connection with, for example, skin contact and / or handpiece motion measures.

  Throughout this specification, the terms “head”, “headpiece” and “handheld device” may be used interchangeably.

  Each of these components is discussed in detail below.

A. Electromagnetic Radiation Source The energy source 210 is any suitable optical energy source capable of generating optical energy of a desired wavelength or a desired wavelength band, or multiple wavelength bands, including interfering and non-interfering sources. Good. The correct energy source 210 and the selection of the correct energy is a function of the type of treatment to be performed, the tissue to be heated, the depth within the tissue where treatment is desired, and the energy absorption of the desired area to be treated. For example, the energy source 210 may be a radiant lamp, a halogen lamp, an incandescent lamp, an arc lamp, a fluorescent lamp, a light emitting diode, a laser (including diodes and fiber lasers), sunlight, or other suitable light energy source. In addition, the same or different energy sources can be used. For example, multiple laser sources can be used, which can generate light energy having the same wavelength or different wavelengths. As another example, multiple lamp sources can be used, which can generate light energy having the same or different wavelength bands through a filter. In addition, different types of sources can be incorporated in the same device, for example both laser and lamp together.

  The energy source 210 can produce electromagnetic radiation, such as near-infrared or visible light radiation over a broad spectrum, limited spectrum, or single wavelength, as produced by a light emitting diode or laser. In one example, a narrow-spectrum source is preferred because the wavelength produced by the energy source can be targeted to a specific tissue type or can be tailored to reach a selected depth. In another aspect, a broad spectrum source is preferred, for example in a system where the wavelength acting on the tissue can be varied, eg by using different filters depending on the application. Sound, RF or other EMF sources can also be used for adapted applications.

  For example, superficial targets such as vascular and pigment disorders, small wrinkles, skin texture, and pores can be treated with UV, purple, blue, green, yellow light, near-infrared light emission (eg 290 ˜600 nm, 1400 to 3000 nm) can be used. Blue, green, yellow, red and near infrared light in the range of about 450 to about 1300 nm can be used to treat targets at a depth of up to about 1 millimeter below the skin. For processing deeper targets (eg, up to about 3 millimeters below the skin surface), using near infrared light in the range of about 800 to about 2350 nm, about 1500 to about 1800 nm, or about 2050 nm to 2350 nm Yes-(see Table 1B).

1. Interfering light source The energy source 210 may be a variety of interfering light sources such as solid state lasers, dye lasers, diode lasers, fiber lasers, or other interfering light sources. For example, the energy source 210 may be a neodymium (Nd) laser such as a Nd: YAG laser. In this exemplary embodiment, energy source 210 includes a neodymium (Nd) laser that generates radiation having a wavelength near 1064 nm. Such a laser forms a lasing medium, such as a neodymium YAG laser rod (YAG main crystal doped with Nd ⁺³ ions) in this embodiment, and an optical resonator for generating laser radiation in conjunction with the laser rod. Related optics (eg mirror). In another embodiment, the treatment radiation can be generated using another laser source, such as chromium (Cr), ytterbium (Yt), or a diode laser, or a broad source such as a lamp.

  Lasers and other interfering light sources can be used to convert wavelengths in the range of 100 to 100,000 nm. Examples of interference energy sources are solids, dyes, fibers, and other types of lasers. For example, a solid state laser using a lamp or diode pumping can be used. The wavelength generated by such a laser is in the range of 400 to 3,500 nm. This range can be extended to 100-20,000 nm by using non-linear transformation. Solid state lasers can provide maximum flexibility with pulse widths ranging from femtoseconds to continuous waves.

  Another example of an interfering light source is a dye laser that uses non-interfering or interference pumping to provide tunable optical radiation. Dye lasers can utilize dyes dissolved in a liquid or solid matrix. Common variable wavelength bands cover laser bandwidths of 400-1200 nm and about 0.1-10 nm. By mixing different pigments, it is possible to emit multiple wavelengths. The conversion efficiency of the dye laser is about 0.1-1% for non-interfering pumping and up to about 80% for interfering pumping. Laser radiation can be delivered to the processing site by an optical waveguide, or in another embodiment, multiple laser sources (lamps) can be used to pump multiple waveguides or laser media in close proximity to the processing site. . Such dye lasers can produce energy exposures of up to several hundred J / cm2, pulse times from a few picoseconds to tens of seconds, and fill rates of about 0.1% to 90%.

Another example of an interference light source is a fiber laser. A fiber laser is an active waveguide (Rahman laser) with a doped or undoped core that provides interference or non-interference pumping. Rare earth metal ions can be used as a doping material. The core and cladding material may be quartz, glass or ceramic. The core diameter may be from a few microns to a few hundred microns. Pumping light is launched into the core through core facets or cladding. The optical conversion efficiency of such a fiber laser reaches a maximum of about 80%, and the wavelength range is about 1,100 to 3,000 nm. Mixing multiple types of rare earth ions with or without the addition of the Raman transformation can generate different wavelengths simultaneously, which is beneficial to the processing results. This area can be expanded with the help of second harmonic generation (SHG) or optical parametric oscillator (OPO) optically coupled to the fiber laser. The light output can be directed to the target with the help of various optical elements described below, or can be in direct contact with the skin with or without a protective / cooling interface window. Such fiber lasers can produce energy exposures of up to about several hundred J / cm ² and pulse times of about several picoseconds to tens of seconds.

  Diode lasers can be used for the range of 400 to 100,000 nm. Since many photodermatological applications require a high-power light source, the configuration described below using a diode laser bar is predicated on a cw diode laser bar of about 10-100 W, 1 cm long. Note that the configuration described for the diode laser bar use case can be replaced with other light sources (eg, LEDs and microlasers) by making corresponding changes to the optical and mechanical subsystems.

  Other types of lasers (eg, gas lasers, excimers, etc.) can also be used.

2. Non-interfering light source Non-interfering light sources of electromagnetic radiation (eg, arc lamps, incandescent lamps, halogen lamps, light bulbs) can be used as the energy source 210 in the present invention. There are several monochromatic lamps available, such as hollow cathode lamps (HCL) and electrodeless discharge lamps (EDL). HCL and EDL can generate emission lines derived from chemical elements. For example, sodium emits bright yellow light at 550 nm. The output radiation can be collected on the target by a reflector and a collector. An energy exposure of about tens of J / cm ² , a pulse time of about a few picoseconds to tens of seconds, and a fill rate of about 1% to 90% can be achieved.

  A linear arc lamp uses, as a light source, a rare gas plasma heated by pulse electric discharge. Commonly used gases are xenon, krypton, and mixtures of various ratios thereof. Filling pressures range from about a few torr to thousands of torr. The lamp envelope for a linear flash lamp can be made from fused silica, doped silica or glass, or sapphire. The emission band is about 180-2,500 nm for a transparent envelope, which can be achieved by appropriately applying doping ion material within the lamp envelope, dielectric coating on the lamp envelope, absorption filter, fluorescence converter, or a suitable combination of these means. It can be changed by selecting.

In some embodiments, a xenon filled linear flash lamp with a trapezoidal collector made of BK7 glass can be used. As described in some aspects below, the distal end of the optical train may be, for example, an array of microprisms attached to the outer surface of the collector. The spectral range of EMR generated from such a lamp is about 300-2000 nm, the energy exposure is up to about 1,000 J / cm ² , and the pulse time is about 0.1 ms to 10 s.

Incandescent lamps are one of the most common light sources and have a radiation band of 300-4,000 nm when the filament temperature is about 2,500 ° C. The output radiation can be collected on the target by a reflector and a collector. Incandescent lamps can achieve about several hundred J / cm ² of energy exposure and pulse times of about several seconds to tens of seconds.

Halogen tungsten lamps utilize a halogen cycle to extend the life of the lamp, which allows operation at high filament temperatures (up to about 3,500 ° C.), which greatly improves optical output. The emission band of such a lamp is in the range of about 300 to 3,000 nm. The output radiation can be collected on the target by a reflector and a collector. Such a lamp can achieve an energy exposure of about several thousand J / cm ² and a pulse time from about 0.2 seconds to continuous radiation.

  Light emitting diodes (LEDs) that emit light in the 290-2,000 nm region can be used to cover wavelengths that cannot be handled directly by diode lasers.

  Referring to FIGS. 3A and 3B, the energy source 210 or the optical system 212 can include a suitable filter that can select, or at least partially select, specific wavelengths or wavelength bands from the energy source 210. In one type of filter, the filter can block a specific set of wavelengths. Undesirable wavelengths within the energy from energy source 210 can be shifted in a manner known in the art to increase the available energy in the desired wavelength band. As such, the filter can include elements that are intended to absorb, reflect or alter specific wavelengths of electromagnetic radiation. For example, a filter can be used to remove certain types of wavelengths that are absorbed by the surrounding tissue. For example, the dermis, subcutaneous tissue and epithelial tissue are mainly made of water, as are other body parts. By using a filter that selectively removes the wavelengths that excite water molecules, the absorption of these wavelengths by the body can be greatly reduced, which reduces the amount of heat generated by the absorption of light into these molecules. Will help. Thus, by passing the radiation through the water-based filter, the frequency of the radiation that excites these water molecules will be absorbed by the water filter and will not be transmitted into the tissue. In this way, the water-based filter can be used to reduce the amount of radiation that is absorbed by the tissue above the treatment area and converted to heat. For other treatments, absorption of radiation by water may be desired or necessary for the treatment.

B. Optical System In general, the optical system of FIGS. 3A and 3B receives radiation from an energy source 210 and directs one or more beams 222 to a selected one or more target portions 214 of volume V. It works to converge / concentrate and the focus is directed to both depth d and space within region A (see FIG. 3B). Some aspects of the invention use such an optical system 212 and other aspects do not use the optical system 212. In some aspects, the optical system 212 produces one or more beams that do not converge or diverge. In embodiments with multiple energy sources, the optical system 212 can focus / concentrate energy from each energy source into one or more beams, each such energy from one energy source, or multiple Only combinations of energy from other energy sources can be included.

  The optical system 212 can be used to concentrate the emitted light energy and deliver more energy to the target portion 214. Depending on the system parameters, the portion 214 can take various shapes and depths as described above.

  An optical system 212 as shown in FIGS. 3A and 3B can simultaneously focus energy into portion 214 or a selected subset of portion 214. Alternatively, the optical system 212 can comprise an optical or mechanical optical scanner for moving radiation focused at depth d to a continuous site 214. In another alternative embodiment, the optical system 212 can produce an output focused on the depth d, and the skin surface on the volume V can be manually or in a suitable 2D or 3D (including depth) The positioning mechanism can be physically moved to direct the radiation to the desired continuous portion 214. For the latter two embodiments, the movement may be performed directly from the focused position to the position, or in a standard predetermined pattern, such as a grid, spiral or other pattern, and the EMR source is above the desired position 214. Operates only when you come to Japan.

  When a sound, RF or other non-optical EMR source is used as the energy source 210, the optical system 212 may be a system suitable for concentrating or converging such EMR, such as a phasing train, and the term “optical system” Is to be interpreted as encompassing such systems where applicable.

C. Cooling Element As noted above, the system 208 can also include a cooling element 215 that cools the surface of the skin 200 on the treatment volume V. As shown in FIGS. 3A and 3B, the cooling element 215 acts on the optical system 212 to cool the portion of the system that is in contact with the patient's skin, thereby allowing the patient to be in contact with such an element. The part of the skin can be cooled. In some inventive embodiments intended for use in the stratum corneum, the cooling element 215 may not be used, or may not be cooled during processing (eg, used only before and / or after processing). In some embodiments, cooling can be applied intermittently between portions of the skin surface (cooling isolated points), eg, optical isolated points. In some embodiments, skin cooling is not required and the cooling element may not be on the handpiece. In another aspect, cooling is applied only to the tissue portion between the process isolation points for clarity of contrast.

  The cooling element 215 can comprise a system for cooling the optical system (and hence the part in contact with the skin) as well as a contact plate that touches the patient's skin during use. The contact plate may be, for example, a flat plate, a series of guide pipes, a covering blanket, or a series of conduits for the passage of air, water, oil, or other fluids or gases. For example, in one embodiment, the cooling system may be a water cooled contact plate. For example, FIG. 6 shows a cooling plate 244 that contacts the patient's skin during use. In another aspect, the cooling mechanism may be a series of conduits that carry a coolant or refrigerant liquid (eg, cryogen) that contacts the patient's skin 200 or the plate of the device 208 that is in contact with the patient's skin. is doing. In yet another aspect, the cooling system may include a water or refrigerant liquid (eg, P134A) spray, cold air spray, or air flow across the surface of the patient's skin 200. In another aspect, cooling can be achieved through chemical reactions (eg, endothermic reactions) or by electrical cooling such as Peltier cooling. In yet another aspect, the cooling mechanism 215 may have more than one type of coolant, or, for example, when the tissue is actively or directly cooled using a cold or other suitable spray, There may be no cooling mechanism 215 and / or contact plate. A sensor or other monitoring device may be incorporated into the cooling mechanism 215 or other part of the handheld device, for example for temperature monitoring or to determine the degree of cooling required by the patient's skin 200, or manually Or you may control electrically.

  In one example, the cooling mechanism 215 can be used to maintain the surface temperature of the patient's skin 200 at a normal temperature, such as 37 or 32 ° C., depending on the type of tissue being heated. In another embodiment, the cooling mechanism 215 can be used to lower the surface temperature of the patient's skin 200 to a temperature below the normal temperature of that type of tissue. For example, the cooling mechanism 215 could reduce the tissue surface temperature to a range of, for example, 25 ° C. to −5 ° C. In other embodiments, the plate can function as a heating plate to heat the patient's skin. Some embodiments can include a heating plate that can be used for cooling and heating.

  The contact plate of the cooling element 215 can be made from a corresponding heat conducting material and, if the plate is in contact with the patient's skin 200, from a material that is optically compatible with the tissue. Sapphire is an example of a suitable material for the contact plate. When the contact plate has a high thermal conductivity, the cooling mechanism 215 can cool the tissue surface. In another aspect, the contact plate may or may not be an integral part of the cooling mechanism 215. As shown in FIGS. 3A and 3B, in some embodiments of the invention, energy from energy source 210 may be passed through the contact plate. In such a structure, the contact plate can be made of a material capable of transmitting at least a portion of the energy, such as glass, sapphire, or transparent plastic. In addition, the contact plate can be made such that a portion of the energy passes through the contact plate, eg, through a series of holes, passages, mask apertures, lenses, etc. in the contact plate. In another aspect of the invention, energy will not pass through the cooling mechanism 215.

  In certain aspects of the invention, various components of the system 208 may need to be cooled. For example, in the embodiment shown in FIGS. 3A and 3B, the energy source 210, the optical system 212, and the filter may be cooled by a cooling mechanism (not shown). The design of the cooling mechanism is related to the components used to assemble the device. The cooling elements 215 for the patient's skin 200 and the cooling elements for the components of the system 208 may be part of the same system, separate systems, or one or both. The cooling mechanism for the components of system 208 may be a corresponding cooling mechanism known in the art. Component cooling can be achieved by convective or conductive cooling. In some embodiments, the cooling element can protect the optical system 212 from overheating due to EMR absorption.

D. Apparatus for creating multiple treatment isolated points Multiple different devices and structures can be used to spatially modulate and / or concentrate EMR to create treatment isolated points on the skin. For example, the apparatus can create a processing isolation point utilizing reflection, refraction, interference, diffraction and deflection of incident light. Some of these devices are briefly described below, but a more detailed description of the device is provided in relation to other parts of the specification, particularly the chapter entitled Device and System for Creating Process Isolation Points, Example 4. Yes. Process isolation point creation methods and many other methods and apparatus for creating process isolation points are described throughout the specification. In addition, several devices and methods for creating process isolation points are described below, but the invention is not limited to these specific methods and devices.

  EMR partitioning using light reflection can be achieved using light spectrum or diffuse reflection from a surface with a refractive index higher than unity. The division of EMR by refraction can be achieved using refraction in an angular plane or aspect. Diffraction division is based on the fact that light can turn around corners. Deflection division can be achieved when light propagates through a medium with a non-uniform refractive index.

1. Partial blockage of the EMR beam In some embodiments, a mask can be used to block a portion of the EMR generated by the EMR source from reaching the tissue. The mask can have multiple holes, lines, and slits, which act to spatially modulate the EMR to create process isolation points. FIGS. 7 and 8 illustrate two embodiments of the invention where the process isolation point is typically made using a mirror with holes or other passable portions. The light passes through the mirror hole and strikes the patient and creates a treatment isolation point. Light reflected by the mirror may remain in the optical system through the reflection system and redirected through the hole to increase efficiency. One effective mask is a contact cooling mask that is highly reflective and minimally absorbable for shielding light (ie, it contacts the skin during processing).

2. Focusing, directing or concentrating the EMR beam In some embodiments, the spatial modulation and concentrating of the EMR can spatially distribute the output light by shaping the light guide end into a prism, pyramid, cone, groove, hemisphere, etc. This can be achieved by modulating and focusing, thereby creating a treatment isolated point on the patient's skin. For example, FIGS. 9A to 10A depict such an embodiment. A number of exemplary imaging and / or diffractive optics types that can be used in this aspect of the invention are described in the section entitled Apparatus and System for Creating Isolated Points (Example 2) below.

  In addition, in some embodiments, as in the embodiments of FIGS. 10A-10C, the end of the light guide is shaped so that light is totally internally reflected when the distal end of the device contacts the air. (TIR), while allowing the EMR to pass when the distal end contacts the lotion or skin surface.

  Alternatively, in some aspects, a spatially modulated phase sequence can be used to cause a phase shift between different portions of the incident beam. As a result of interference between the parts, amplitude modulation is produced in the output beam.

3.EMR source array
Instead of splitting the EMR into multiple beams, multiple isolated light sources or a single light source equipped with a serial or parallel optical multiplexer can be used to create treatment isolated points on human skin. For example, the embodiment of FIG. 11 uses a line or array of non-interfering EMR sources to create a processing isolated point. Another embodiment of the present invention as shown in FIG. 12C uses a diode laser bar to form process isolated points. In yet another embodiment, a bundle of optical fibers is used to deliver spatially modulated EMR to the patient's skin. 12E, 13B-D and 14A are exemplary embodiments using bundles of optical fibers.

4. EMR Source Pulsing In some embodiments, the invention can include a sensor for measuring a hand piece motion measure across a target area of the patient's skin. The handpiece may further include a communication circuit with the sensor to control the light energy to create a processing isolation point. The circuit can control the pulsing of the light energy source based on a motion measure of the head portion across the skin, for example, to create a process isolation point. In another aspect, the circuit moves the motion of a mechanism within the device so that the head moves over the skin to create a process isolation point and only a specific area of the skin is exposed to EMR energy. Can be controlled based on a motion measure of the head portion across the skin. Figures 15 and 16 are exemplary embodiments of this aspect of the invention.

5. Exogenous chromophore lattice In another embodiment, the spatially selected treatment isolated points can be created by applying a topical composition containing an exogenous chromophore that exhibits favorable absorption in a desired pattern. it can. The chromophore can also be introduced into the tissue using a needle, such as a microneedle as used in tattooing. In this example, EMR energy may be applied to the entire skin surface to which such a pattern of topical composition has been applied. When the appropriate EMR is applied, the chromophore heats up, thereby creating a treatment isolated point on the skin. In the present invention, various substances such as carbon, metals (Au, Ag, Fe, etc.), organic dyes (methylene blue, toluidine blue, etc.), non-organic dyes, nanoparticles (like fullerene), nanoparticles with shells, carbon fibers, etc. Can be used as a chromophore, but is not limited thereto. The desired pattern may be random and need not be regular or predetermined. It may vary depending on the skin condition of the desired treatment area and may be drawn on the fly.

  In some embodiments, the invention provides a film or substrate having a grid of dots, lines or other shapes embedded in the film surface or film, the dots, lines or other shapes being suitable for an EMR source Contains a chromophore. The dots, lines, or other shapes may or may not be the same size, and the film may include other shapes.

  The dots, lines, or other shapes may be made from materials that can be glued, welded or otherwise bonded to the stratum corneum to create isolated points, and such bonds can peel the film from the skin. However, at the same time, dots, lines or other shapes can be left on the skin. For example, a dot, line or other shape can be peeled off before applying the EMR energy when the film is applied to the skin and when UV light is applied to the film, the dot, line or other shape will bind to the skin. It can be made from such an ultraviolet curable compound. In another example, the dots, lines or other shapes can be made from a suitable phase change material (eg, aluminum) that can be used for welding. In another example, the film is not peeled off and EMR energy is applied through the film.

  Alternatively, the dots, lines, or other shapes are conventionally applied individually to the skin or applied by spraying or other techniques. In another embodiment, the handpiece is used to add shape to the skin before applying EMR energy. As one example, the shape may be included in other topical compositions that are applied to the skin by hand before applying EMR energy using a lotion, gel, powder or handpiece. Alternatively, the handpiece may be used to apply lotion before delivering the EMR energy with the handpiece. As another example, a film containing the shape may be applied to the skin using a hand or handheld device (eg, a tape dispenser).

6. Creation of a thermal grid using pattern cooling Some embodiments can create a thermal (and damaged) grid (or process isolated points) by using a uniform EMR beam and a spatially modulated cooling device. The thermal grid produced in such an example would be reversed with respect to the original cooling matrix.

E. Controllers and Feedback Systems Some embodiments of the invention can also include measure sensors, contact sensors, imaging arrays, and controllers that assist in various functions that apply EMR to the patient's skin. The system 208 of FIG. 3A includes a photodetector 216, which may be, for example, a capacitive imaging array, a CCD camera, a photodetector, or other detector suitable for the selected patient's skin characteristics. The output from detector 216 is sent to controller 218, which is typically a microprocessor or similar circuit programmed accordingly, but special purpose hardware or hardware and software. It may be a hybrid. The controller 218 can control the activation and deactivation of, for example, the light source 210 or other mechanism for illuminating the skin (eg, a shutter), or the controller 218 can also control the power profile of the radiation. The controller 218 can also be used, for example, to control the depth of focus of the optical system 212 and to control the location 214 where the radiation is focused / concentrated at some point. Furthermore, the controller 218 can control the cooling element 215 and can be used to control both the skin temperature and the cooling temperature above the volume V both before cooling and during irradiation.

F. Creation of gratings using non-optical EMR sources The inventive gratings can also be made using non-optical sources. For example, as described above, microwave, high frequency and low frequency, or DC EMR sources can be used as energy sources to create a grid of EMR-processed isolated points. In addition, in order to treat the tissue surface, the tissue surface can be brought into direct contact with a heating element with a desired grid pattern.

  The following examples illustrate some preferred modes of carrying out the invention, but are not intended to limit the scope of the claimed invention. Similar results could be obtained using different materials and methods.

Isolated and isolated point computer and theoretical models The optical, thermal and damaged isolated point models described above were analyzed using a computer model. The beam can be focused inside the skin to create a three-dimensional optical isolation point below the skin surface and to limit it from each direction. A three-dimensional heat or damage isolated point under the skin surface can be created by using a three-dimensional optical isolated point or by using skin surface cooling in combination with an optical beam including a converted, divergent or collimated beam. On the other hand, two-dimensional and one-dimensional isolated points below the skin surface can be obtained using a parallel beam with a normal incidence angle on the skin surface. For this reason, the effects of both parallel and focused beams were taken into account. Furthermore, the procedure emphasised herein is one in which heat and damage isolation points are believed to be due to light absorption by tissue water rather than due to other chromophores (ie, melanin and hemoglobin). This mechanism is characteristic for processing in the near infrared (NIR) region. As a standard example, type II skin according to the classification of Fitzpatrick (Fitzpatrick (1998), Arch. Dermatol. 124: 869-71) was used, and the wavelength of light was assumed to be 800 nm or more. The light pulse is generally assumed to be rectangular.

  To manipulate the periodicity of isolated points, the correspondence between voxels (ie, periodically repeating cells that form a grid, each cell containing one isolated point and the space surrounding the isolated point) Periodic boundary conditions related to light and temperature were applied to the interface. More precisely, the voxel interface was considered as an adiabatic surface exhibiting complete refraction of light. This technique allows the solution of the light transport equation and the heat equation to be evaluated within a single voxel, which can then be regularly spread across the lattice.

A. Computer Model of Skin As shown in FIG. 63, the skin is approximated by a flat four-layer structure showing cylindrical symmetry. Specific phases included in the model are the upper layer incorporating the stratum corneum, and the upper three layers of the epithelium: the epithelial basal layer, the reticular dermis with the upper vascular plexus, and the dermis.

In the visible and NIR spectral regions, the absorption coefficient of each layer is affected by three basic chromophores: blood, melanin and water. This can be written as:
Where k = 1 ... 4 is the layer number and M _k , B _k and W _k are the volume fractions of melanin, blood and water melanin in the layer (Mk is summarized for the melanin containing layer) Yes, including upper and basal layers, and M _k is zero for the other layers), C _k is the correction factor, μab (λ), μaM (λ), μaW (λ) and μaT (λ) Are the absorption coefficients for blood, melanin, water and background tissue absorption, respectively. The latter absorption coefficient is independent of wavelength and is suggested to be equal to 0.015 mm ⁻¹ . This value is obtained from a comparison between the measured spectrum and the theoretical spectrum of skin reflection around 800 nm, and the absorption of the three main chromophores is very small.

  The correction factor is a number from zero to a unit that takes into account the fact that the blood is not uniformly distributed throughout the tissue but is limited to blood vessels. If the blood vessel is thick enough, the light will not reach it and therefore the inside of the blood vessel will not act as an absorber. In such a case, the correction factor will be clearly less than one unit. Conversely, for very thin blood vessels, the correction factor is close to the unit element. Therefore, the correction factor depends on the average diameter of the blood vessel and the absorption coefficient of blood at a specific wavelength. In order to evaluate these coefficients, numerical data from (Verkrysse et al. (1997), Physics in Medicine and Biology 42: 51-65) were used.

Several publications deal with blood absorption spectra (eg Roggan et al. (1999), Biomedical Optics 4: 36-46; Yaroslavsky et al. (1996), Proc. SPIE 2678: 314-24; Svaasand et al. (1995), Lasers in Medical Science 10: 55-65). The generally accepted relationships are as follows:
Where H is the hematocrit value (ie, the percentage of blood volume occupied by red blood cells), OS is the oxygen saturation, and μaHb (λ) and μaHbO ₂ (λ) are the absorption coefficients depending on the wavelengths of hemoglobin and oxyhemoglobin, respectively. . In the present invention, as general values, 0.4 is used for hematocrit and 0.8 is used for OS, and the latter is an average value of venous blood (0.7) and arterial blood (0.9). Second, the absorption spectrum of hemoglobin and oxyhemoglobin could be approximated by the sum of the Gaussian bands. The intensity and width of the band can be found in (Douven et al. (2000), Proc SPIE 3914: 312-23).

For turbid media, if blood is present, it affects the scattering coefficient of the layer. The effect of blood on the total scattering coefficient is derived by the following correlation (Douven et al. (2000), Proc SPIE 3914: 312-23):
The total scattering coefficient of blood at this time is obtained from the following equation:
Also, the anisotropy factor of blood scatter is assumed to be constant throughout the visible and NIR wavelength ranges:

The total scattering coefficient of bloodless tissue, μsTκ, decreases with increasing wavelength. Several empirical relationships describing this dependence have been reported in the literature (Douven et al. (2000), Proc SPIE 3914: 312-23; Jacques (1996) In Advances in Optical Imaging and Photon Migration eds. Alfano et al. 2: 364-71). These relationships collapse beyond 1000 nm, where the decrease in scattering coefficient is very slow (Troy et al. (2001), Journal of Biomedical Optics 6: 167-176). To cover both the visible and NIR regions, the formula representing the total scatter coefficient of bloodless tissue was rearranged as follows:
Here, μsOκ is the scattering coefficient at the reference wavelength of 577 nm listed in Table 1.

Scattering anisotropy was expressed to include blood involvement in the same manner as equation (A3):
Here, gT (λ) is an anisotropy coefficient of bloodless tissue. The latter factor is an increasing function of wavelengths shorter than 1000 nm, and measurements using integrating sphere techniques suggest that gt (λ) does not exceed 0.9 for 1000 nm <λ <1900 nm (Troy et al. ( 2001), Journal of Biomedical Optics 6: 167-176). Therefore, in order to describe the wavelength dependence of the anisotropy coefficient of bloodless tissue, the corresponding equation from (Tsai et al. (1999), Proc. SPIE 3601: 327-334) is gt (λ) = 0.9 And obtained the following formula:

Melanin is completely confined to the epithelium, and its overall concentration depends on the type of skin. In the relationship of the four-layer model used in the present invention, the layers containing melanin are two layers: the upper layer and the basal layer. This distribution of melanin between the two layers also depends on the type of skin. In whitish skin, melanin is mainly confined to the basal layer, whereas in dark skin the distribution of melanin within the epithelium is slightly more uniform. The melanin fraction of the basal layer is estimated to be 50% for skin types V and VI and 70% for other skin types (Fitzpatrick (1998), Arch. Dermatol. 124: 869-71). The total amount of melanin is characterized by the optical density (OD) of the epithelium, the product of the melanin absorption coefficient and the epithelial thickness. In the model described by the present invention, the total OD is the sum of the contributions of the upper and basal layers. Although the OD fluctuated due to many factors such as sunburn, the general OD listed in Table 1 was used here. These values are adjusted to the reference wavelength λ _th = 800 nm.

The OD of melanin in the infrared can be described by the following relationship:

  The absorption spectra of water in the visible and near IR can be found in the literature (Hale et al. (1973), Applied Optics 12: 555-63; Querry et al. (1978), Applied Optics 17: 3587-92). The volume fraction of water in the skin layer is listed in Table 1. The refractive index of the layers is assumed to be constant throughout the visible and NIR regions and is listed in Table 1.

  The thermal parameters of the skin layer are related to Takata (Takata et al. (1977) Laser induced thermal damage in skin. Report SAM-TR-77-38 Brooks Air Force Base (X: US Air Force School for Aero-space Medicine) ) To obtain soft tissue density, specific heat, and thermal conductivity as a function of water content. The values obtained from this usage are listed in Table 1 along with the thermal parameters of the sapphire window.

The extent of damage was quantified by comparing it to a fraction of intact, but coagulated tissue at a specific site. If c (t) is the rate of time t in an undamaged tissue, c (0) = 1. The rate of solidified tissue is represented by 1-c (t). From the kinetic model of tissue damage, the relationship
Was obtained, but in the formula
F (T) is a function of absolute temperature (Kelvin temperature) called damage function (Pearce et al. (1995), In Optical-thermal response of laser-irradiated tissue eds. Welch et al. (NY and London: Plenum Press) pp.561-606). The damage function used in this study is as follows (Pearce et al. (1995) In Optical-thermal response of laser-irradiated tissue eds. Welch et al. (NY and London: Plenum Press) pp.561-606; Henriques (1947), Arch. Pathol. 43: 480-502; Henriques et al. (1947), Am. J. Pathol. 23: 531-49; Moritz et al. (1947), Am. J. Pathol. 23 : 695-720; Wright (2003), J. Biomech, Eng. 125: 300-04):
Where R = 8.31 J / (mole-K) is the general gas constant, A is the rate constant, and Ea is the activation energy of the solidification process. Assuming the damage function (A10), the Arrhenius damage integral is obtained:
This is a measure of the degree of damage (Pearce et al. (1995) In Optical-thermal response of laser-irradiated tissue eds. Welch et al. (NY and London: Plenum Press) pp. 561-606). The apparent disadvantage of using this scale is that the Arrhenius integral becomes infinite when the tissue is fully coagulated, ie c (t) → 0. A more practical measure used herein is the change in the relative rate of undamaged tissue: Ω ₁ = [c (0) −c (t)] / c (0) = 1−exp (−Ω) . The latter parameter is always positive and never exceeds the unit. Obviously Ω ₁ = 0 indicates no damage, while Ω ₁ = 1 means that the tissue is fully coagulated. It is worth noting that the parameters Ω ₁ and Ω are very close when the degree of damage is small compared to the unit element. The parameter values used in the simulation are as follows: A = 3.1 · 10 ⁹⁸ s ⁻¹ and Ea = 6.28 · 10 ⁵ J / mole (Pearce et al. (1995) In Optical-thermal response of laser -irradiated tissue eds. Welch et al. (NY and London: Plenum Press) pp.561-606).

B. Theoretical Model of Isolated Lattice Relaxation The theory of selective photothermal decomposition considers the target time required to reach thermal equilibrium with its environment when the target overheats the relaxation time (TRT) of each target. TRT is d ² / (8α), d for planar (one-dimensional), cylindrical (two-dimensional) and spherical (three-dimensional) targets where d is the target width (one-dimensional) or diameter (secondary or three-dimensional) ² / (16α), and d ² / (24α).

  This definition can be extended to an isolated lattice. Obviously, if the grid is very scattered, ie if the fill factor is much less than 1, the LTRT is approximately equal to the TRT of the individual isolated points. However, it is expected that dense grids not only reach equilibrium more quickly than scattered grids, but LTRT is mainly determined from the number of dimensions of the grid, its packing factor and the isolated point TRT.

The exact definition of LTRT was formulated as follows: The isolated point was heated to temperature T _{0 at} zero zero time, with the tissue temperature T _b <T ₀ . If no external action is applied, the temperature gradient in the lattice will disappear with time and will reach a thermal equilibrium state T _st = T _b + (T ₀ -T _b ) · f in the stationary phase. Since the time to reach steady temperature cannot be infinite, LTRT is the time required for the isolated point to cool to an intermediate temperature
Where e is the natural logarithmic root.

LTRT depends on the lattice filling factor f, and can be drawn by considering a two-dimensional lattice as a specific example. Neglecting the exact voxel influence and isolated point shape, the isolated point and voxel can be assumed to be cylinders with radii r ₀ and R = r ₀ / √f, respectively. Obviously, the cylindrical pattern cannot be spatially expanded into a lattice. However, by transforming an actual voxel into a cylinder with the same cross-sectional area, the LTRT can be transformed into an evaluable form. The significance of this transformation is to reduce the number of problem dimensions to one. The time-dependent heat equation in a cylindrical voxel was solved mathematically by applying a periodic (symmetric) boundary condition to its outer surface.

Therefore, the heat equation, initial conditions and boundary conditions in a cylindrical frame can be written as follows:
Here, ρ, c and κ are tissue density, specific heat and thermal conductivity. T _b = 0 suggests that this does not limit the universality of the analysis. Infinite time τ = t / TRT and infinite coordinates
(At this time
Is the TRT of a cylinder isolated point, α = κ / (ρc) is the thermal diffusivity) and the following equation is obtained:
Equations (A15) to (A17) are numerically solved to determine the LTRT, that is, the temperature at the voxel center.
The time to go down can be evaluated. It is worth noting that the set of (A15)-(A17) is linear with respect to temperature, and that LTRT does not depend on its initial temperature. As a result, the ratio of LTRT to isolated point TRT depends only on the lattice filling factor. This simplification obviously comes from assumptions made to reduce the dimensionality of the problem.

C. Lattice temperature relaxation time (LTRT)
In order to obtain a lattice of thermal isolated points (LTI), a corresponding optical isolated point (LOI) lattice must first be created. The next step is to create a pulse width that is short enough to avoid overlap with adjacent thermal isolation points. It should be emphasized that the LTI is a time-dependent structure, and this latter requirement means that the isolated points must not overlap during the week when the temperature reaches its maximum.

Limitations on pulse width are specified in the theory of selective photothermal decomposition (Anderson et al. (1983), Science 220: 524-26; Altshuler et al. (2001), Lasers in Surgery and Medicine 29: 416-32). In its original formulation, this theory deals with isolated targets in the tissue. The theory points out that it is possible to selectively heat the target if the pulse width is smaller than what is the time interval characteristic of the target and is called the temperature relaxation time (TRT). TRT is essentially the target cooling time, which is the time required to cool an immediately superheated target to 1 / e of its initial temperature. This concept can be easily applied to individual isolated points. The TRT of a planar isolated point (tissue layer, one dimensional) is d ² / (8α), where d and α are the target width and tissue thermal conductivity, respectively. For cylinder (two-dimensional) and sphere (three-dimensional) targets, the relevant relationship is: d ² / (16α) and d ² / (24α), where d is the diameter of the isolated point (Altshuler et al. (2001), Lasers in Surgery and Medicine 29: 416-32). This concept has been generalized to periodic gratings of optical isolated points as discussed below.

  It is assumed that the temperature dynamics of the lattice are dependent on the relationship between the isolated point and the area of the vexel rather than the exact shape of the isolated point and the vector. This is effective when the vexel is not extremely anisotropic, i.e. not long in one direction and short in another. An anisotropic lattice can then be considered as a lattice with a smaller dimensionality. Specifically, if the voxel is a very narrow rectangle, reduce the number of dimensions of the grid from 2 to 1: Change this rectangle to one that is the same width but infinite length Can be a one-dimensional lattice.

The thermodynamics of LTI depend on how the LOI is introduced into the skin. The first method is “continuous method” or “continuous LOI”. In this case, at any moment, exactly one (or a plurality of distant) optical isolation points are created in the tissue. A continuous LOI can be made using a laser beam scanner. The second method is “parallel method” or “parallel LOI”. In this case, a plurality of optical isolation points are created simultaneously in the tissue during the light pulse. The thermal interaction between isolated points of continuous LOI is minimal. In the case of parallel LOI, the thermal interaction between different isolated points can be very meaningful. For parallel LOI, the assumptions for assessing the thermal relaxation time (LTRT) of the lattice are the same as for finding the TRT for each isolated point. The isolated point is instantaneously heated to the temperature T ₀ while maintaining the other space at the contact background temperature T _b <T ₀ . By conducting heat to the surrounding tissue and cooling the isolated points, the lattice becomes a steady-state temperature depending on the filling factor.
Will head for the thermal equilibrium. LTRT is the characteristic cooling time until the temperature of the isolated point (more precisely, the maximum temperature within the isolated point) reaches an intermediate value between the initial temperature and the equilibrium temperature:
Can be defined as

  Employing this definition, the LTRT of a highly scattered grid is equal to the TRT of individual isolated points. For such a grid, each isolated point cools independently of other isolated points. However, for denser grids, the temperature profile of the different isolated points overlaps, lowering the LTRT. This cooperative hardening was examined by evaluating the ratio of LTRT to TRT as a function of filling rate, using a grid of cylindrical isolated points as a specific example, as described herein. LTRT increases monotonically with increasing filling factor. Therefore, the denser the lattice of isolated points, the shorter the time it takes for the lattice to reach thermal equilibrium with the surrounding tissue and relax. When the filling rate reaches the unit element, the LTRT is close to the TRT but slightly larger. This difference is due to the difference between the LTRT definition used herein and the normal definition of TRT. True temperature delay is not exponential due to heating of the surrounding tissue. Therefore, the time required for the target to reach its temperature at 1 / e of the initial value is always longer than TRT, which is the actual upper limit of LTRT (LTRT is Approaching the limit).

As an approximation of the dependence of the ratio of LTRT to TRT on the filling factor, the following simple relation can be used:
The fit to the numerical data for f> 0.1 was good. In practice, equation (A24) means that LTRT is proportional to the time interval, Δ ² / (2-α), but at the same time the thermal tip covers the distance between isolated points Δ = d / √f Yes. If the voxel size is much larger than the diameter of the isolated point, the contrast of the thermal grid will be reduced before the thermal tip covers the distance Δ. Therefore, equation (A24) overestimates LTRT when f <0.1.

D. Optical fluence parameters for isolated point formation in tissue To obtain isolated isolated points, the incident fluence must be constrained up and down: F _min <F <F _max . The second half of the equation means that the fluence must be large enough to provide the desired effect on the isolated point, but insufficient to have the same effect on the entire tissue. In practice, the right side of the inequality is sufficient to avoid the bulk effect for all examples, while the left side is short only when the pulse width is short and the relationship between the transmitted light energy and the resulting action is local. It compensates for the formation of isolated points. This means that the effect depends on the total radiation dose applied to the same point in the tissue, not the average of the radiation applied to the same region of tissue. However, in the case of longer pulses, this dependence becomes non-localized due to heat and mass transfer within the tissue (Sekins et al. (1990) In Therapeutic Heat and Cold, 4-th edition Ed Lehmann (Baltimore: Williams & Wilkins) pp.62-112). Therefore, isolated points may not appear even if the left side of the inequality is maintained. F _min can be found as the fluence required to heat the tissue within the isolated point to a threshold temperature T _tr at which the tissue solidifies. If the pulse width is short enough and heat conduction is negligible, the threshold fluence for protein coagulation is given by:
Where ρ is the skin density, c is the specific heat, μ _a is the skin absorption coefficient, and T _i is the initial temperature. The threshold for large scale damage F _max is the fluence required to heat the tissue, both isolated and between isolated points, to a threshold temperature. Since the volume of this tissue is 1 / f times larger than the volume occupied by the isolated point, the following equation is derived:

This equation is based on the assumption that the treatment is safe as long as the tissue between isolated points is sufficiently intact and recovery is compensated. A more conservative premise is that in addition to this first criterion, the process is safe until the temperature of the isolated point reaches the thermomechanical action threshold, T _max . In this case, the following equation is derived:

The first criterion anticipates significant safety gaps. For example, if f = 0.25, the isolated points and the space between them have equal safety margins, F _max / F _min = 4. The second criterion is more restrictive. In the case of skin, T _max can be determined as the evaporation temperature of water, T _max = 100 ° C. The protein coagulation temperature with a pulse width in the millisecond range is T _tr = 67 ° C. Therefore, according to the second criterion, the safety margin F _max / F _min = 2.1.

  A large safety margin is one of the most important features of the grid method. The above safety estimate applies to periodic (regular) lattices. If the grid is irregular, the isolated points may overlap, creating a large damaged area. This is the main reason for focusing on the regular lattice in future analyses.

  Consider an isolated point in front of a grid of isolated points. A common way to create a three-dimensional (stereoscopic) optical isolation point is to focus the light inside the skin. If the numerical aperture (NA) of the input beam is large enough, an optically isolated point with high contrast will be obtained. However, if the NA is too large, light tapping and waveguide propagation in the epithelium with a higher refractive index than the underlying dermis can be expected.

E. Dependence of threshold fluence on wavelength The threshold fluence F _min for isolated point processing always depends on the wavelength. This type of specific anteriority is illustrated in Figure 64, which shows spatially limited type II skin thermal damage caused by a 0.1 mm diameter collimated light pulse applied to the skin through sapphire. Show. The pulse width was assumed to be sufficiently short (so-called adiabatic mode) that leakage of heat energy other than the treatment site can be ignored during the pulse. If the isolated point is a cylinder with a diameter of d = 0.1 mm, the temperature relaxation time is TRT = d ² / (16-α) · 10 ms, where α · 10 ^-3 cm ^-2 s ^-1 is thermally diffusive. is there. The threshold light fluence is the light incident on the evaluated skin, which heats the tissue to 30 ° C at a characteristic depth of 0.5 mm (curve 1), 0.5 mm (curve 2) and 0.75 mm (curve), respectively. The tissue to that depth was coagulated. The low threshold fluence region in FIG. 64 corresponds to the absorption peak of tissue water.

The low threshold fluence region near 970 nm is consistent with the weak water absorption peak. However, the other minimum is off the water absorption peak, and this shift is an increasing function of the damage depth. The reason is that the low threshold fluence is always halfway between strong absorption and weak dimming in the skin. The lowest threshold for damage at depths of 0.25 mm, 0.5 mm and 0.75 mm is observed at 1450 nm, 1410 and 1405 nm, respectively. As can be seen in FIG. 64, the threshold fluence depends on the depth of tissue damage. The threshold behavior of the damage spectrum F _th (λ) is very similar at all depths except in the range of 1400-1600 nm. In this range, the damage spectrum F _th (λ) has the same minimum for depths of 0.25 mm and 0.5 mm. For deeper damage (0.75mm), Fth (λ) is the optimum wavelength for deeper vertical cylindrical damage isolation points with two minimum values (1405nm and 1530nm) and one maximum value (1480nm). is doing.

  An important feature of plot 1-3 in FIG. 64 is that the threshold fluence gradually decreases toward the longer wavelength, which leads to a decrease in the tissue scattering coefficient. In fact, the massive scattering that scatters the narrow beam reduces the irradiance of the tissue while propagating through the skin. In general, when the wavelength exceeds 1200 nm, the scattering coefficient of the skin layer becomes relatively small, which provides an opportunity to create a perfectly shaped cylindrical damage isolated point to a rather low fluence. Another problem is the relationship between the minimum of curves 1-3 and the maximum absorption of tissue water.

  It is useful to compare the penetration depth spectrum of FIG. 65 with the threshold fluence spectrum of FIG. The comparison suggests that the deeper penetrating wavelengths do not need to be optimized in terms of maximizing the effects of heat. Instead, the optimal wavelength at a depth must be chosen to maximize the product of irradiance (at the depth in question) and the absorption coefficient. For depths up to 0.75 mm, it is reasonable to use wavelengths in the range of 1200-1800 n because it is outside the strong absorption peak of water and the scattering of light within the tissue is relatively small.

  In shallow depth processing (up to 0.75mm), a parallel beam with a diameter of about 0.1 can be used efficiently to create LOL. In order to protect the stratum corneum and epithelium from damage, it is possible to take advantage of the low water content of the stratum corneum and epithelium compared to the dermis by using wavelengths that are highly absorbed by water (approximately 1.45, 1.9 μm). it can. In addition, it is also possible to selectively cool the stratum corneum and epithelium. For deeper targets within the dermis and subcutaneous tissue, large sized optical isolation points must be used.

F. Formation of Optical Isolated Point Using Focusing Method FIG. 66 illustrates the formation of a three-dimensional optical isolated point using the focusing method. The figure shows the distribution calculated for the on-axis skin irradiance of a uniform beam focused to the depth of 0.5 mm inside the skin of type II (Fitzpatrick (1998), Arch. Dermatol. 124: 869-71). Show. The beam diameter is 1 mm, so the numerical aperture is 1. Skin irradiance was normalized for incident light fluence at the skin / sapphire interface. Curves 1-6 were obtained for specific wavelengths using the four-layer skin model described in the present invention. Each curve shows a deep peak at the depth of focus-the so-called ballistic focus. This peak is broadened by multiple scattering due to microscopic skin heterogeneity such as cell membranes, mitochondria, cell nuclei and the like. The ballistic focus itself is formed by the part of the photon that reaches the depth of focus without scattering. The contribution of ballistic photons to the total energy balance is very small; however, these photons are collected in a narrow region of the focal spot and form a sharp irradiance peak. Therefore, the size of the latter area and the height of the ballistic peak are determined from the ballistic light aberrations based on macroscopic changes in the refractive index of the skin. The skin model described herein uses a different index of refraction for each layer and assumes that the interlayer boundary is a plane. Since the true layer boundary is bent, the aberration is larger than the flat boundary. Therefore, this model may overestimate the height of the ballistic peak. Another problem is the size of mesh elements used in Monte Carlo simulation. In fact, the Monte Carlo operation of the present invention evaluates the average irradiance within the vortex rather than the local irradiance at a point. The size of the mesh element used this time was 10 μm in both directions. Smaller elements were not used because the light transport theory does not account for microscopic irradiance oscillations and that the voxel size must be much larger than the wavelength.

  Most of the incident photons do not contribute to the ballistic peak itself because it causes multiple scattering. However, post-scattering is extremely anisotropic in the NIR region. This means that the direction of the scattered photon is strongly correlated with its initial direction. For this reason, the irradiance distribution produced by the radiated light may be somewhat closer to the distribution produced by the ballistic light. In particular, a peak with high irradiance of scattered irradiation may appear much wider than the ballistic peak near the focal point, or may appear with much more light energy. The combined (ballistic and scattering) peak near the focal point is called the “geometric focal point”. The magnitude of the maximum irradiance in the focus will be small if the scattering coefficient is focused too far or too deep for a particular wavelength.

G. Correlation between irradiance and depth of focus The maximum value of irradiance near the focus gradually decreases as the depth of focus increases. At the same time, a weak peak of irradiance appears above the focus. The latter peak is called "diffuse focus". This is illustrated in Figure 67, where a sapphire is used to focus 1064nm light to a depth of 0.5 (1), 0.6 (2), 0.7 (3) and 1 (4) mm inside the skin. Analyzing. In later examples, the geometric focus can hardly be recognized, while the “diffuse” focus is clearly seen.

  The irradiance profile inside the skin is determined by two competing processes: geometric transformation in large tissue and divergence due to multiple scattering of light. The scattering coefficient gradually decreases as the wavelength increases.

H. Monte Carlo Simulation of Light Transport A planar or cylindrical optical isolated point that is perpendicular to the skin surface can be obtained by using a narrow parallel light beam on the skin. A beam is considered collimated if it does not converge or diverge in a non-scattering space having the same refractive index as the skin refractive index Z _{0 at the} treatment depth. The minimum diameter of the collimated beam can be found from the following equation (Yariv (1989) Quantum Electronics (NY: John Wiley and Sons)):
Where λ is the wavelength. At typical depths, Z ₀ = 1 mm and λ = 1500 nm, d _min = 0.1 mm. The spot profile is a line (stripe) for a one-dimensional isolated point and a limited shape such as a circle or a square for a two-dimensional isolated point. For a circular light beam with a diameter of 100 μm (wavelength 1200 nm) applied to the skin through sapphire, the transverse intensity profile of the beam is flat at shallow depths and shifts to a Gaussian distribution as it goes deeper into the skin. Therefore, the optical isolation point has a clear circular shape at the top and is slightly blurred at the bottom. The following demonstrates that if the pulse is sufficiently short, weak divergence outside the original cylinder does not contribute to tissue damage. This opens an opportunity to create a very isolated cylindrical isolated point of damage.

I. Effect of beam diameter and wavelength on penetration depth In assessing the shape of isolated points, it is important to explain the effect of beam diameter on the penetration depth of light through the skin. The penetration depth is defined as the depth of the tissue where the illumination intensity is 1 / e of the fluence incident on the skin surface. This effect has been well studied for a wider, typically 1 mm beam (Klavuhn (2000) Illumination geometry: the Importance of laser beam spatial characteristics Laser hair removal technical note No 2 (Published by Lumenis Inc)). However, if the beam diameter is only a few tens of micrometers, much shorter than the diffusion length of light in the skin, the propagation dynamics will be significantly different from the wide beam. Specifically, with such a narrow beam, the irradiance decreases monotonously as it moves deeper into the skin along the beam axis, whereas with a wide beam the irradiance may be maximized below the surface. is there. This is illustrated in FIG. 68, where plots 1 and 2 are for a wide beam (diameter 10 mm) and narrow beam (diameter 0.1 mm) at a wavelength of 1060 nm. In this regard, it should be noted that the total amount of irradiance at the skin is the sum of the direct and scattered components, and the maximum below the surface is solely due to the scattered components. As the beam diameter becomes smaller, the on-axis irradiance becomes mainly composed of direct components, and the maximum value below the surface disappears.

  FIG. 65 shows the wavelength dependence of the transmission depth of a uniform circular beam with an incident diameter of 0.1 mm. This dependence appears to be rather flat as opposed to wide beam (Jacques et al. (1995) In Optical-thermal response of laser-irradiated tissue eds. Welch et al. (NY and London: Plenum Press ) Pp. 561-606; Jacques (1996) In Advances in Optical Imaging and Photon Migration eds. Alfano et al. 2: 364-71; Anderson et al. (1994), Proc. SPIE MS-102: 29-35) . The maximum variation rate of penetration depth in the specified range is only 30-35%. The penetration depth is limited by water absorption and tissue scattering. Obviously, the scattering effect is stronger with the narrow beam than with the wide beam. Scattering by tissue decreases with increasing wavelength, but water absorption increases. Since these two effects partially offset, the net variation in penetration depth is rather small.

J. Damage Generation Dynamics Damage isolated point grids are generated from thermal isolated point grids when certain restrictions on pulse width and flux are met. Damage kinetics follows Arrhenius equation. The relationship between temperature and damage isolated point is not linear. Although different tissue sites show the same peak temperature, the degree of damage varies depending on the time that the temperature is maintained above the activation threshold of the coagulation reaction. Furthermore, when the pulse width is small, the temperature isolated point can be made very sharp at the end of the pulse. In this case, after extinguishing the light, the isolated point may expand due to a steep temperature gradient, and the surrounding tissue may be damaged. The effect of such expansion leads to the occurrence of major damage if the filling rate rises beyond the safety limit.

  LOI technology has some fundamental differences and potential advantages over conventional processing, which uses a uniform light beam to heat and damage bulky tissue. From computer and theoretical models of isolated points and lattice formation, the following conclusions were reached:

  (1) In addition to the conventional parameters that characterize light processing such as wavelength, fluence, pulse width and spot size, two new important factors were introduced: filling rate (fractional volume) and isolated point size. Furthermore, the resulting therapeutic effect may be affected by the geometry (shape, symmetry) and dimensionality of the grid and isolated points. LOI can be introduced at various depths of the organization. For example, in skin, the LOI can be placed in the stratum corneum, epithelium, dermis, or subcutaneous tissue. For deep LOIs, focusing techniques and selective surface cooling can be used. The wavelength range suitable for LOI treatment is the near infrared region (900 to 3000 nm), and water functions as the main target chromophore.

(2) The main potential advantage of the LOI method over the conventional method is that the safety margin between the therapeutic effect threshold and the unwanted side effect threshold is significantly higher. The safety margin is defined as F _max / F _min , where F _min is the desired therapeutic effect threshold and F _max is the continuous major injury threshold. The theoretical upper limit of the safety margin is 1 / f, where f is the lattice filling factor. In practice, the safety margin is determined by the formula F _max = F _min · (T _max -T _i ) / (T _tr -T _i ), where T _max is the water evaporation temperature and T _rt is the treatment It is the lowest temperature that can still provide the effect. This margin can be increased up to twice as much as in the case of conventional photothermal treatment. Furthermore, it must be emphasized that the periodicity of the grating is important in keeping the safety margin stable and in maintaining the reproducibility of the results.

  (3) The efficiency of grid processing can be increased by reducing the size of isolated points and maximizing the grid filling rate. Small sized spherical or elliptical isolated points can be created with minimal irradiance by using a focusing technique with a large numerical aperture for wavelengths in the 900-1800 nm region and skin depths up to 0.7 mm. The position of the optical isolation point corresponds to the ballistic focus. At deeper focusing, the ballistic focus disappears and the maximum irradiance stabilizes at a depth of ~ 0.5 mm (diffuse focus).

(4) A small cylindrical isolated point can be created in the tissue by using a parallel microbeam. The confocal parameter of such a beam must be longer than the depth of the cylinder in the tissue. For depths greater than 0.5 mm, the microbeam diameter is generally greater than 0.1 mm. In contrast to the broad beam, the penetration depth of the microbeam is relatively insensitive to wavelengths in the 800-1800 nm region. However, the threshold fluence of tissue damage is strongly dependent on wavelength. The minimum threshold fluence can be found in the range of 1380-1570 nm. The resulting depth of the cylinder can be controlled by fluence. For superficial cylinders with a depth of 0.25 to 0.5 mm, the minimum threshold fluence can be obtained in the wavelength range of 1400 to 1420 nm, the absolute value of this fluence being 12 to 80 J / cm ² . For deeper transmission cylinders with a depth of 0.75 mm, the minimum threshold fluence can be found at 1405 nm (400 J / cm ² ) and 1530 nm (570 J / cm ² ). In principle, the LOI can be made to a depth of a few millimeters in the tissue, but in this case the size of the isolated point will also reach a few millimeters.

  (5) The degree of optical damage is determined by the size and fluence of the optical isolation point. The damaged isolated point overlaps the original optical isolated point if the pulse width is the minimum effect fluence. At larger fluences, the damaged isolated points may expand in size even after the light pulse has ended, resulting in an LTI fill factor, LDI greater than the original LOI fill factor. The isolated points of the grating can be created in the tissue continuously using a scanner or simultaneously using a grating of light beams. For the latter, the optimum pulse width is shorter than the lattice thermal relaxation time and is approximately given by LTRT = TRT / 3f, where LTRT and TRT are the LOI thermal relaxation time and the single isolated point thermal relaxation time, respectively. is there.

  The optical isolated point grid concept can be used in dermatology, dentistry, ophthalmology, and other biomedical applications where the target of treatment is sufficiently superficial as a safe and effective treatment modality. The same concept can be applied to other energy sources such as microwave, high frequency, and ultrasonic waves.

Apparatus and System for Creating Isolated Points One embodiment of the invention has been described above in conjunction with FIGS. 3A and 3B. The following types of lenses and other focusing optics can be used with such embodiments.

Lenses and Other Focusing Elements FIGS. 19A-27C illustrate various systems for delivering radiation in parallel to multiple target sites 214. These shaped arrays are generally arranged with a fixed focus at a particular depth d. This depth can be varied by using another array with a different depth of focus, by selectively changing the position of the array relative to the patient's skin surface or target volume V, or by controlling the amplitude-phase distribution of the incident radiation. Can do. FIGS. 28-31 illustrate an array of various optical lenses that can be used with the scanning or deflection system of FIGS. 32A-37 to continuously move one or more focal portions 214 within the target volume V. FIGS. . Finally, FIGS. 38 and 39 show two types of variable convergence optical systems that can be moved over the patient's skin, for example, mechanically or manually, to demonstrate a continuous portion 214 thereon.

A. Convergence element FIGS. 19A-C show a convergence element 1 on a substrate 3, which comprises a hexagonal pattern (FIG. 19A), a square pattern (FIG. 19B) and a circular or elliptical pattern ( FIG. 19C). Standard optical materials can be used for these elements. The hexagonal and square patterns can completely fill the working area of the converging element plate 4, but not the element pattern of FIG. 19C. The radiation from the radiation source 210 is generally applied to all the converging elements 1 simultaneously; however, the radiation can be applied to these elements continuously by using a corresponding scanning mechanism or in one direction. It is also possible to scan and illuminate / illuminate, for example, four elements at a time.

B. Microlens System FIGS. 20A and 20B are cross-sectional views of a microlens system incorporated in a refractive material 8, such as porous glass. The refractive index of the material of the lens 5 must be greater than the refractive index of the refractive material 8. In FIG. B2, the beam 11 first passes through the flat surface 10 of the refractive material 8 and then is refracted by the primary surface 6 and secondary surface 7 of each microlens 5 and the beam converges to the focal point 12. In Figure B2A, this process is reversed, but the result is the same. In FIGS. 20C and 20D, the incident beam 11 is refracted by a primary lens surface 6 made of a refractive material 8. For various arrays, surfaces 6 and 7 may be spherical or aspheric.

C. Lenses and Arrays of Lenses in Immersion Material In FIGS. 21A and 21B, lens piece 15 is mounted on a substrate and is in immersion material 16. The refractive index of the lens piece 15 is larger than the refractive index of the immersion material 16. The liquefied material 16 can be in gas (air), liquid (water, cryospray) or can be used to cool the skin using a corresponding solid gas or liquid. The immersion material is generally present on the primary and secondary flat surfaces 13 and 14, respectively. The depth of focus can be adjusted by changing the refractive index of the immersion material. In FIG. 21B, the primary surface 6 and the secondary surface 7 of each lens piece 15 can achieve higher quality convergence. In FIGS. 21C and 21D, the lens piece 15 is fixed on the surface of the refractive material 8, and in the embodiment of FIG. 21D, the depth of focus of FIG. 21C, or the other arrays shown in FIGS. 21B-21D for the lens 15 shown. Gives a deeper focus than the depth of focus. The lens array shown in FIGS. 21B-21D is a preferred lens array for the practice of the teachings of the present invention.

D. Fresnel Lens FIGS. 22A-D show the surfaces 17 and 18 of a Fresnel lens made of refractive material 8. By changing the profile of the Fresnel lens surfaces 17 and 18, the relationship between the Fresnel surface center 17 and the radius of the ring 18, the desired quality of focusing can be achieved. The arrays of FIGS. 22C and 22D allow for achieving high quality focusing and are another preferred array. Surfaces 17 and 18 may be spherical or aspheric.

E. Holographic Lens and Spatial Modulation Phase Array In FIGS. 23A and 23B, focusing of the incident beam 11 is achieved by shaping a holographic lens 19 on the surface of the refractive material 8. The holographic lens 19 can be formed on one or both surfaces of the refractive material 8, as shown in FIGS. 23A and 23B. FIG. 23C shows a holographic material 20 that replaces the refractive material 8 of FIGS. 23A and 23B. The holographic lens is shaped within the volume of material 20.

  Techniques other than holography can be used to induce phase variations at various locations of the incident beam, thereby changing the amplitude of the output beam.

F. Tilting Lens In FIGS. 24A and 24B, the converging element is formed by a tilting lens 22 having a primary plane 23 and a secondary plane 24. As shown in FIG. 24B, such a tilting lens may be sandwiched between a set of refractive material plates 8 that provide support, protection and possibly cooling to the lens.

G. Cylindrical Lenses FIGS. 25A, 25B and 25C illustrate various matrix arrays of cylindrical lenses 25. FIG. The relationship between the length 26 and the diameter 27 of the cylindrical lens 25 varies as shown in the figure. The cylindrical lens 25 of FIGS. 25B and 25C provides a linear focus rather than a spot or circular focus like the array shown above.

  26A-26D are cross-sectional views of one layer of a matrix cylindrical lens system. Incident beam 11 is refracted by cylindrical lens 25 (FIGS. 26A and 26B) or semi-cylindrical lens 29 (FIGS. 26C and 26D) and converges to linear focal point 28. In FIGS. 26C and 26D, the cylindrical lens 29 is in the immersion material 16. The primary working optical surface 30 and the secondary working optical surface 31 may be circular or elliptical, so that high quality convergence can be achieved. As shown in FIGS. 25A-26D, the linear focus for adjacent lenses can be directed in various directions, but the directions are perpendicular to each other in these figures.

  In FIGS. 27A, 27B and 27C, the focal matrix is obtained by passing the incident beam 11 through two layers of cylindrical lenses 32 and 35. 27B and 27C are two orthogonal cross-sectional views of the array shown in FIG. 27A. By changing the focal length of the primary layer lens 32 having the surface 33 and the secondary lens 35 having the surface 36, an orthogonal focal point of a desired size can be obtained. The primary layer lens 32 and the secondary layer lens 35 are mounted in the immersion material 16. Lenses 32 and 35 may be standard optical fibers or may be replaced with cylindrical lenses, which may be circular or elliptical. Surfaces 34 and 37 are of optical quality that minimizes edge loss.

  The optical system can be used with a pulsed laser (0.1-100 ms) to simultaneously introduce a grid of optical isolated points into the skin. For example, it may be an Er: glass laser (1.56 micron wavelength) or an Nd: YAG laser (1.44 micron) with a fiber delivery system and imaging optics to homogenize the beam before the focusing element.

H.1, 2 or 3 Objective Lenses FIG. 28 shows a single objective lens 43 with a beam splitter 38. The beam 11 incident on the oblique beam splitter (phase mask) 38 is split, passes through the refracting surfaces 41 and 42 of the next lens 43, and is focused on the center point 39 and the point 40 deviated from the center. Surfaces 41 and 42 may be spherical and / or aspheric. A plate 54 having optically flat surfaces 53 and 55 maintains a constant distance between the optical surface 55 and the focal points 39,40. The oblique beam splitter 38 can act as an optical diffraction grating and splits the beam 11 into multiple beams to provide multiple convergence.

  In FIG. 29, two objective lenses 43, 46 provide high quality convergence and numerical aperture by optimally positioning optical surfaces 41, 42 and 44. All of these surfaces may be spherical or aspherical. The optical surface 45 of the lens 46 may be planar to increase the numerical aperture or may be in contact with the plate 54. The plate 54 may be a cooling element as described above.

  FIG. 30 differs from the previous figure in that it includes three objective lenses and lenses 43, 46, and 49. FIG. FIG. 31 shows a four objective lens system, with optical surfaces 50 and 51 of lens 52 allowing the radius of the processing area (ie the distance between points 39 and 40) to be increased.

I. Optical System with Built-in Mirrors FIGS. 32A, 32B, and 32C illustrate three types of optical systems that can be used as scanning front ends of various objective lenses shown in FIGS. In these drawings, the collimated initial beam 11 strikes the scanning mirror 62 and is reflected by this mirror to the surface 41 of the first lens 43 of the objective optical system. The scanning mirror 62 is designed to move the optical axis 63 in the range of the angle f. By cyclically displacing the perpendicular 64 of the mirror 62 to the angle f, the angle of the beam 11 is changed to the angle 2f. The optical position of the scanning mirror 62 is within the entrance pupil of the focus objective. In order to better associate the scanning mirror 62 with the radius of the work surface (ie the distance between points 39 and 40) and improve the quality of convergence, a lens 58 is inserted in front of the scanning mirror 62 as shown in FIG. 32B. May be. Optical surfaces 56 and 57 of lens 58 may be spherical or aspheric. In order to further control the aberration, a lens 61 may be inserted between the lens 58 and the mirror 62, which has optical surfaces 59 and 60.

  33A, 33B and 33C are similar to FIGS. 32A, 32B and 32C except that the light source is not a collimated beam 11 but a point source or optical fiber. A beam 66 from a point drop 65, such as the end of the fiber, is incident on the scanning mirror 62 (FIG. 33A) or the surface 57 of the lens 58 (FIGS. 33B and 33C).

J. Scanning System FIGS. 34A and 34B show a two-mirror scanning system. In the simpler example shown in FIG. 34A, the scanning mirror 67 rotates in the range of the angle f2, and the scanning mirror 62 rotates in the range of the angle f1. The beam 63 first enters the mirror 67, is reflected toward the mirror 62 by the mirror 67, and is then reflected toward the surface 41 of the optical lens 43. In FIG. 34B, the objective lens 106 is inserted between the mirrors to increase the numerical aperture of the focused beam, increase the work area on the skin, and reduce the aberrations of the scanning mirrors 62 and 67. In this figure, a simple objective lens 106 is depicted, but a more complex objective lens system can also be used. The objective lens 106 reflects the beam from the center of the scanning mirror 67 toward the center of the scanning mirror 62.

  In FIG. 35, the scanning is performed by the scanning lens 70, but the scanning lens can move in the direction s. When the scanning lens 70 moves toward the off-center position 73, the optical surface 68 reflects the light beam in the direction 72 along the optical axis 71.

  In FIG. 36, the scanning is performed by rotating the lens 76 in the direction of the position 77, for example. Surface 74 is flat and surface 75 is chosen so as not to affect the direction of reflected optical axis 72. In FIG. 37, scanning is performed by dot reduction or moving the optical fiber 65 in a fixed direction.

K. Zoom Objective Lens FIGS. 38 and 39 show a zoom objective lens for moving the damage isolated point to different depths. In FIG. 38, the first component is a single lens 81 that can move in the optical axis direction with respect to the second component, and the second component is fixed and consists of two lenses 84 and 87. . The lens 84 is used to increase the numerical aperture. In order to increase the numerical aperture, increase the back focal length, and reduce the focal spot size, the optical surfaces 79, 80, 82, 83 and 85 may be aspheric. The depth of the focal point 12 is determined by the relative positions of the first component and the second component.

  FIG. 39 shows a zoom objective lens system with a spherical optical surface. The first component is composed of a single lens 90 that can move in the optical axis direction with respect to the second component. The second component is fixed and consists of five lenses 93, 96, 99, 102 and 105. The radii of curvature of the surfaces 88 and 89 are chosen to correct the fixed second component aberration. Again, the depth of focus can be controlled by controlling the distance between the first component and the second component. Both of the lens systems shown in FIGS. 38 and 39 selectively converge on the desired location 214 of the target volume V or non-selectively converge on the position of the target volume V, either manually or under the control of the control 218. Can be installed as you can move.

I. Depth of focus As can be seen in Table B1, the depth d of the volume V and the depth of focus of the optical system 212 are substantially the same when converging to a shallow depth, but generally the skin In the case of a scattering medium such as the above, in order to converge to a deeper depth d, it is necessary to converge to a deeper depth and sometimes to a considerable depth. This prevents the focus from densely converging and minimizing the spot size, thereby concentrating the energy to the maximum, so that the convergent beam is effectively at a depth above where it should originally converge. This is due to the existence. The depth of focus can be selected based on known properties of the skin so that a minimum spot size is obtained at the desired depth d.

M. Wavelength Both scattering and absorption are wavelength dependent. Therefore, at a shallow depth, a convergent beam can be obtained even when using a very wide range of wavelengths. Narrower. Table B1 shows preferred wavelength bands for various depths, but other bands can be tolerated but not optimal.

N. Pulse width Normally, the pulse width of the radiation used is shorter than the thermal relaxation time (TRT) of each target site at the optical isolation point 214. If longer than this time, does heat move across the boundary of these sites? It is. Since portion 214 is generally relatively small, the pulse duration will also be relatively short. However, as the depth increases, the resulting spot size increases and the maximum pulse width or period also increases. If the target density is not so high, the pulse width will be longer than the thermal relaxation time of the target site 214 and the total heat from the target area at a point outside the target area will be less than the tissue damage threshold at that point. Also goes far below. Generally, thermal diffusion theory, the pulse width tau spherical isolated point is τ <500D ^2/24, although the pulse width of the cylindrical isolated point diameter D indicates that it is τ <50D ^2/16 D in this case is the characteristic size of the target. Furthermore, the pulse width can sometimes be longer than the thermal relaxation time of the target site if the target density is not very high, and the total heat from the target region 214 at some point outside the target region is It is well below the tissue damage threshold at that point. Again, as discussed later, with the proper cooling process, the above limitations may not apply and a pulse time exceeding the thermal relaxation time, sometimes exceeding the TRT, may be available for the damaged site 214.

O. Power The power required of the radiation source depends on the desired therapeutic effect and increases with increasing depth and cooling, and decreasing absorption with wavelength. The power also decreases with increasing pulse width.

P. Cooling Generally, the cooling device 215 is activated prior to the source 210 to deepen the patient's skin to protect at least the DE junction 206, preferably the skin region 220 above the volume V. Precool to selected temperature below normal skin temperature, eg, -5 ° C to 10 ° C, until d. However, according to the teachings of the present invention, if the pre-cooling time is long enough to cool the patient's skin deeper than volume V, especially if cooling continues after the start of radiation, heating is only applied to the radiation site 214. Occurring and each site will be surrounded by cooled skin. Therefore, even if the length of applied radiation exceeds the TRT at sites 214, heat from these sites will be contained and thermal damage will not occur beyond these sites. Furthermore, the nerves at site 214 are stimulated, but in addition to being able to tightly control the volume of injury, cooling these nerves outside site 214 also blocks the transmission of pain signals to the brain. Can be treated more comfortably, allowing radiation that allows the desired treatment, which is otherwise impossible for the patient to feel pain. This cooling management is an important feature of the present invention.

Q. Numerical Aperture The numerical aperture is a function of the angle 9 of the focused radiation beam 222 from the optical device 212. This number, and therefore the angle 9, is as large as possible, so that the energy of the region 214 where the radiation in the volume V is collected is substantially greater than the other sites in the volume V (and region 220), thereby causing the region 220 It is preferable that a desired therapeutic effect can be achieved at the position 214 within the volume V while minimizing damage to the tissue within and the site within the volume V other than the site 214. The larger the numerical aperture of the beam, the higher the safety of the epithelium, but the numerical aperture is limited by the scattering and absorption of light rays with a large incidence angle. As can be seen in Table B1, the possible numerical aperture decreases with increasing depth of focus.

In Vitro Porcine Skin Transmission Channels and Increased Optical Clearness The grid of damaged isolated points is a standard flash arc lamp system (StarLux Rs®, Palomar Medical Technologies, Burlington, MA), and made of film-like carbon particles and made into the skin stratum corneum of domestic pigs using a wound isolated point mask used on the skin surface. Furthermore, a 40% glucose aqueous solution was applied to the specimen surface to determine the optical clarity of the treated area of the pig skin specimen. Optical clarity refers to a change in the optical properties of a tissue that makes the optical region more transparent by reducing light scattering. Glucose or glycerin penetration into the skin increases optical clarity by reducing the refractive index difference between the interstitial solution and the intracellular matrix proteins collagen and elastin.

In the first set of experiments, approximately 4 m ² of livestock pig skin specimens were adhered to a hard, transparent substrate (LOCTITE 411 glue) and wiped clean with alcohol cotton. The dried skin surface was divided into four 1 cm ² areas. A damaged isolated point mask was placed on the surface of the specimen and covered with a thin layer of lotion (LuxLotion®, Palomar Medical Technologies, Burlington, Mass.) To improve optical coupling to the light source. Two 36 J / cm ² pulses were applied to two of the four 1 cm ² areas of the specimen using a StarLux Rs handpiece (time 20 seconds). One 20 cm / cm ² pulse was applied twice to one 1 cm ² area of the specimen (time 10 seconds). The 1 cm ² area of the fourth specimen was an untreated control. The distance between the treatment areas was about 1 cm. After the treatment, free carbon particles on the surface were removed, and the test body was covered with 40% glucose solution and kept warm using a hair dryer. Fresh glucose solution was added to keep the sample surface moist.

  After treatment, a thin blue wire was placed under the test area of the test specimen and the appearance of the blue wire through the test specimen was examined to assess the optical clarity of the tissue.

  Photographs of skin specimens were taken for 75 minutes before treatment (FIG. 52), immediately after treatment, and every 15 minutes after treatment. After the treatment, the carbon particles were removed and a photograph of the cleaned sample was taken.

The above-mentioned lattice method of damaged isolated points produced damaged isolated points that could barely be seen in the skin testicle stratum corneum of domestic pigs (FIG. 53). The highest optical clarity was observed 60 minutes after a 36 J / cm ² light pulse (time 20 seconds). The light pulse at 36 J / cm ² (time 20 seconds) achieved better clarity than the pulse at 20 J / cm ² (time 10 seconds). There was no detectable clarity in the control (untreated) area of the specimen (see FIG. 54).

  A grid of heat-damaged isolated points was created in vitro in the stratum corneum of skin specimens of domestic pigs. Thermally damaged isolated points (ie, enhanced permeation pathways) were significantly more optically clear than untreated areas, demonstrating that the skin permeability was enhanced by locally applied glucose.

In the second set of experiments, about 4 m ² of livestock pig skin specimens were adhered to a hard transparent substrate as described above, wiped clean with alcohol cotton, and a damaged isolated point mask was applied to the specimen surface. Placed and covered with a thin layer of lotion. A pulse of 36 J / cm ² and 20 ms was given once to two adjacent approximately 1 cm ² specimen regions. After the treatment, the carbon particles were removed and the specimen was covered with 40% glucose aqueous solution and kept at room temperature for 1 hour. During this time, the specimen was warmed twice at about 40 degrees for 2-3 minutes. After one hour, another 36 J / cm ² , 20 ms pulse was applied twice to one of the treatment areas. The carbon particles were removed and the specimens were covered with 40% glucose solution and kept warm with a hair dryer. The surface of the sample was kept moist with fresh glucose solution as needed. Approximately 2 hours after treatment, optical clarity was assessed by visual observation and recorded as a photograph (see FIGS. 55 and 56).

The specimen area treated with 36 J / cm ² pulses (20 ms) three times showed complete optical clarity, whereas the untreated area lacked clarity. The specimen area treated once with a pulse of 36 J / cm ² (20 ms) showed only partial optical clarity, whereas the untreated area lacked clarity.

Increased human skin permeation channels and optical clarity in vitro Damaged isolated point grids, flash arc lamp system (StarLux Rs®, Palomar Medical Technologies, Burlington, MA) and damaged isolation as described above A point mask was used to create in the human test substance stratum corneum in vivo. Furthermore, in order to determine the optical clarity of the treated area of the skin specimen, a 40% glucose aqueous solution was applied to the specimen surface.

  The tattoo part of the subject's right foot was wiped clean with alcohol cotton and dried. The pre-treated skin area was photographed (Figure 57), the flashpiece lamp system handpiece aperture was covered with a thin layer of lotion (LuxLotion (R), Palomar Medical Technologies, Burlington, MA) and through a damaged isolated point mask. The selected skin area was laser treated.

Pain tolerance testing was performed by applying pulses continuously to selected skin sites while gradually increasing the fluence. The damaged spot mask was placed on the dry skin surface and covered with a thin layer of lotion. Pain tolerance testing was performed on both sites with and without tattoos, and the maximum tolerance fluence was used for treatment. For tattooed sites, ^two 10 J / cm ² pulses (10 ms), two 18 J / cm ² pulses (10 ms), and ^two 24 J / cm ² pulses (20 ms) were tested. The skin areas that do not contain the entered skin area tattoo, 24J / cm ² pulse (20 ms) 2 times, the pulse (20ms) 30J / cm ^{2 2} times and 36J / cm ² pulse (20 ms) 3 times Was tested.

Two skin sites with tattoos were treated with ^two 18 J / cm ² pulses (10 ms) and two 24 J / cm ² pulses (20 ms). Three skin sites without tattoos were treated with ² pulses of 30 J / cm ² (20 ms), 2 pulses of 24 J / cm ² (20 ms), and 3 pulses of 36 J / cm ² (20 ms) . (See Figure 58). The selected skin area was wiped clean with alcohol cotton after each treatment and photographed.

  The subject's tattooed skin area was covered with a layer of dressing sponge soaked with 40% aqueous glucose and kept warm with a hair dryer. The dressing sponge was kept moist by adding fresh glucose solution every 1-2 minutes and changed every 5 minutes. Photographs of the treated areas were taken every 15 minutes for 90 minutes. Optical clarity and stratum corneum isolated points were evaluated by visual observation using a magnifying glass.

  The subject was applied with glycerin cream to treat the test area. Photographs of treated skin sites were taken at 6, 9, 24 and 48 hours after treatment. After 48 hours, the skin area was covered with a layer of dressing sponge moistened with 40% glucose solution and kept warm with a hair dryer. As before, the dressing sponge was kept moist by adding fresh glucose solution every 1-2 minutes and changed every 5 minutes. Photographs of the treated areas were taken every 20 minutes for 60 minutes. Optical clarity and stratum corneum isolated points were evaluated by visual observation using a magnifying glass.

In the above procedure for creating a damaged isolated point grid, both the 30 J / cm ² pulse (20 ms) and the 36 J / cm ² pulse (20 ms) 3 times were treated with the subject's unskinned skin. Clear lesion isolated points were created in the stratum corneum at the site (FIGS. 59A and 59B). In the tattooed area, no clear isolated point of damage was observed 90 minutes after irradiation (FIGS. 59C and 59D). At 90 minutes, no clear optical clarity was observed in the treated area.

At 6, 9, 24 and 48 hours, the lattice of damaged isolated points became clearer. The entered area of skin with a tattoo to be able to clearly define at 6 hours after irradiation (Fig. 60), the area treated three 36J / cm ² pulse (20 ms) edema has occurred (Fig. 61 ).

At 48 hours after treatment, the region treated with 3 pulses of 36 J / cm ² (20 ms) was more reddish (FIG. 62). Redness was interpreted as the result of increased optical clarity by the application of glycerin cream by the subject, thereby increasing the visibility of blood vessels in the dermis. Treating the skin area with 40% glucose solution 48 hours after EMR treatment did not further improve the optical clarity.

The procedure for creating a damaged isolated point grid is good, with normal skin treated with 36 J / cm ² pulses (20 ms) three times, and with tattooed skin treated twice with 24 J / cm ² pulses (20) The pain tolerance limit was shown. The method produced in vivo isolated spots that could be visually confirmed in selected human skin areas, and the isolated spots became more definitive over 6 hours. In vivo treatment of glycerin cream on human skin injury sites with 3 pulses of 36 J / cm ² (20 ms) resulted in optical clarity as evidenced by increased blood vessel visibility.

Apparatus and system for creating treated isolation points Numerous and diverse devices and structures can be used to create treated isolation points in the skin. FIG. 40 illustrates one system for creating treatment isolation points on the skin 280. Applicator 282 has a handle attached so that its head 284 can approach or contact skin 280 and scan over skin 280 in direction 286. The applicator 282 creates a pattern of placement 290 of isolated point particles 292 on the surface of the hyperpermeability region or the skin 280 in the SC, and generates a permeation enhancement pattern when subjected to EMR processing from the applicator 210 A pattern generator 288 can be provided. In one embodiment, the generating device 288 generates heat, damage or photochemical isolated points in the epithelium or dermis.

  In one embodiment, the applicator 282 includes a motion detector 294 that senses scanning of the head 284 with respect to the skin surface 296. The information emitted by this detector is used by the isolated point pattern generator 288 to reliably produce the desired fill rate or isolated point density and power on the skin surface 296. For example, when the scanning speed of the head 284 is fast, the pattern generation apparatus responds by making the generation of isolated points faster. In the following description, this and other aspects of the invention will be described in more detail. Further, the following section details the types of EMR sources that can be used with applicator 282 and methods and structures that can be used to create process isolation points.

A. Handpiece with Diode Laser Bar Some embodiments of the invention use one or more diode laser bars as the EMR source. Because many photodermatological applications require high power light sources, in some embodiments, a standard 40 W, 1 cm long, cw diode laser bar can be used. Any suitable diode laser bar can be used, including, for example, a 10-100 W diode laser bar. Any type of diode laser as described above can be used within the scope of the invention. The diode laser bar can be replaced with other sources (eg, diode laser with LED and SHG) by appropriate modification of the optical and mechanical subsystems.

  FIG. 12A shows one embodiment of the invention using a diode laser bar. Many other embodiments can be used within the scope of the invention. In this embodiment, the handpiece 310 includes a housing 313, a diode laser bar 315, and a cooling or heating plate 317. The housing 313 supports the diode laser bar 315 and the cooling or heating plate 317, and the housing 313 can also support a control mechanism such as a firing button of the diode laser bar 315. The housing 313 can be made from any compatible material including, for example, plastic. The cooling plate, when used, can remove heat from the patient's skin. If used, the heating plate can heat the patient's skin. The same plate can be used for heating or cooling depending on whether a heat source or a cooling source is applied to the plate.

  The diode laser bar 315, in one embodiment, has 10-50 radiation sources (in some embodiments 50-150 μm wide) spaced 50-900 μm apart along a 1 cm long diode bar. Or in another embodiment, having a width of 100 to 150 μm). In another embodiment, more or less than 50 radiation sources can be placed on the diode laser bar 315, and the spacing of the radiation sources and the length of the diode laser bar 315 can be varied. In addition, the width of the radiation source can be changed. The spacing of the radiation sources and the number of radiation sources can be customized during the manufacturing process.

  The diode laser bars 315, in one embodiment, are positioned along a 1 cm long diode bar, each spaced about 50-900 microns in some embodiments and about 500 microns in another embodiment. There are 25 radiation sources with a width of 100 to 150 μm or 50 to 150 μm. 17 and 18 are a top view and a cross-sectional view, respectively, of such a diode laser bar assembly of the present embodiment. In this embodiment, 25 radiation sources 702 are placed directly under the surface plate 704 that is placed in contact with the skin during treatment. Two electrodes 706 are arranged on both sides of the radiation source 702. The bottom of the diode assembly contains a diode laser and a coolant 708 for controlling the temperature of the plate 704.

  In the embodiment of FIGS. 17 and 18, the beam emitted from radiation source 702 diverges in the range of 6-12 degrees along one axis (slow axis) and in the range of 60-90 degrees along the fast axis. The plate 704 can serve as a cooling or heating surface and also serves to place the radiation source 702 in a close proximity near the surface of the tissue to be treated. The distance between the radiation source 702 and the plate 704 is sufficient to minimize or prevent distortion effects on the laser beam without using any optics, for low cost and simplified manufacturing. It may be in the range of about 50 to 1000 micrometers, and in some embodiments, particularly in the range of about 100 to 1000 micrometers. In use, the distance between the radiation source 702 and the patient's skin is about 50-1000 micrometers, and in some embodiments, more particularly 100-1000 micrometers. In such an embodiment, imaging optics are not required, but other embodiments may include additional optics that image the radiation source surface 702 directly onto the tissue surface. In another embodiment, more or less than 25 radiation sources can be placed on the diode laser bar and the length of the diode laser bar can be varied. In addition to this, the width of the radiation source and the light divergence can also be varied. The spacing of the radiation sources and the number of radiation sources can be customized during the manufacturing process.

  FIG. 12B is a perspective view of one embodiment of a diode laser bar 330 that can be used for the diode laser bar 315 of FIG. 12A. The diode laser bar 330 has a length L of about 1 cm, a width W of about 1 mm, and a thickness T of about 0.0015 mm. FIG. 12B depicts twelve radiation sources 332, each emitting radiation 334 as shown in FIG. 12B. The diode laser bar 330 can be placed inside the apparatus 310 of FIG. 12A so that the side S of the diode laser bar 315 faces in the direction shown in FIG. 12A. As a result, the radiation source emits radiation downward toward the skin 319 in the embodiment of FIG. 12A.

  Turning again to FIG. 12A, the plate 317 may be of any type that allows light from the EMR source to pass through the plate 317 as described above. In one embodiment, the plate 317 may be a thin sapphire plate. In another embodiment, another optical material with good optical transparency and high thermal conductivity / diffusivity, such as diamond, can be used for the plate 317. Plate 317 can be used to isolate diode laser bar 315 from patient skin 319 during use. In addition, the plate 317 can cool or heat the patient's skin, if desired. The area where the plate 317 touches the patient's skin can be referred to as the processing window. The diode laser bar 315 can be placed inside the housing 313 so that the radiation source is in close proximity to the plate 317 and thus close to the patient's skin during use.

  In operation, one way to create a process isolation point is to place a housing 313 containing a diode laser bar 315 in close proximity to the skin and then fire a laser. Wavelengths close to 1750-2000 nm, and wavelengths in the range of 1400-1600 nm can be used in methods that create treated isolation points below the surface with minimal effects on the epithelium due to strong water absorption. To create isolated points at or below the skin, in some embodiments, wavelengths of 290-10,000 can be used, while in other embodiments, a wavelength range of 900-10,000 nm can be used. Treatment isolated points can be created in the skin continuously along the line without moving the handpiece across the skin. FIG. 40 shows the placement of isolated points on one possible skin 280 surface using such a diode laser bar, in which case the diode laser bar 315 is moved over the skin in direction A of FIG. 12A. While applying the pulse.

  In another aspect, the user can simply touch the target skin area with the handpiece and continuously fire a diode laser to create a continuous treatment line while moving the handpiece over the skin. For example, using the diode laser bar 330 of FIG. 12B, the treatment line will appear on the skin (one line for each radiation source).

  In another aspect, an optical fiber can be coupled to the output of each radiation source of the diode laser bar. In such embodiments, the diode laser bar need not be in close proximity to the skin during use. Instead, the optical fiber couples light from the radiation source to the plate, which is in close proximity to the skin during use.

  FIG. 12C shows another embodiment of the invention, which uses a plurality of diode laser bars to create a matrix of process isolated points. As seen in FIG. 12C, a plurality of diode laser bars can be arranged to create a collection of bars 325. In FIG. 12C, for example, bar assembly 325 includes five diode laser bars. The bar assembly 325 can be mounted in the housing 313 of the handpiece H101 having a firing source in close proximity to the cooling plate 317 in a manner similar to that described above with respect to FIG. 12A.

  In operation, the handpiece 310 of FIG. 12C is carried close to the skin surface 319 and the cooling plate 317 is brought into contact with the skin. The user can simply move the handpiece over the skin and the diode laser can be pulsed to create a matrix of treated isolated points in the skin. The firing wavelengths of the collecting bars need not be the same. In some embodiments, it may be advantageous to mix different wavelength bars in the same set to achieve the desired therapeutic result. By selecting bars that emit different wavelengths, the depth of penetration can be changed and, as a result, the depth of the spot of the processing isolated point can also be changed. Thus, the process isolated point lines or spots created by the individual bars can be located at different depths.

  In operation, the user of the handpiece 310 of FIG. 12A or 12C brings the handpiece processing window into contact with the first position on the skin, fires the diode laser bar at the first position, and then places the handpiece on the skin. The firing can be repeated by contacting the second position above.

  In addition to the above embodiment of placing the diode laser bar close to the skin surface and creating a treatment isolation point, the diode laser bar can be coupled to the skin using various optical systems. For example, looking at FIGS. 12A and 12C, the imaging optics can be used to re-image the firing source on the skin surface, thereby providing a gap between the diode laser bar 315 (or bar assembly 325) and the cooling plate 317. It becomes possible to take in space. In another embodiment, the diffractive optics can be placed between the diode laser bar 315 and the power carrier (ie, the cooling plate 317) to create an arbitrary matrix of processing spots. Various exemplary types of imaging optics and / or diffractive optics that can be used in this aspect of the invention are described in the section entitled Apparatus and System for Creating Isolated Points (Example 2) above. Has been.

  Another embodiment of the invention is depicted in FIG. 2D. In this embodiment, the housing 313 of the handpiece 310 includes a collection of diode laser bars and a plate 317 as in the previous embodiment. However, this embodiment also includes four diffractive optical elements 330 disposed between the assembly 250 and the plate 317. In another embodiment, more or fewer than four diffractive optical elements 330 can be provided. The diffractive optical element 330 can diffract and / or focus the energy from the assembly 325 to form a pattern of treated isolated points in the skin 319. In one aspect of the invention, one or more motors 334 for moving the diffractive optical element 330 are provided in the handpiece 310. The motor 334 may be any suitable motor including, for example, a linear motor or a piezoelectric motor. In one embodiment, the motor 334 can move one or more diffractive optical elements 330 horizontally, so that these elements 330 are no longer in the optical path and there is only one (or possibly more) in the optical path. Only the diffractive optical element 330 is left. In another aspect, the motor 334 can move the one or more diffractive optical elements 330 in the vertical direction to change the beam convergence.

  In operation, more than one diffractive optical system 330 is incorporated into the handpiece 310 with a motor 334 for moving different diffractive optical systems 330 between the diode laser bar assembly 325 and the plate 317. Can be moved at a position between the assembly 325 and the cooling plate 317, and energy can be converged into various patterns. Thus, in such an embodiment, the user can select from various patterns of skin treatment isolated points using the same handpiece 310. To take advantage of this aspect of the invention, the user can place the handpiece 310 on the target area of the skin before firing, as in the previous aspect. In another aspect, the handpiece aperture need not touch the skin. In such an aspect, the handpiece may comprise a standoff (not shown) for establishing a predetermined distance between the handpiece aperture and the skin surface.

  FIG. 12E shows another embodiment of the invention. In this embodiment, optical fiber 340 is used to couple light to the output / aperture of handpiece 301. Therefore, a diode laser bar (or a collection of diode laser bars or other light sources) can be placed in the base unit or in the handpiece 301 itself. In either case, the optical fiber couples light to the output / aperture of the handpiece 310.

  In the embodiment of FIG. 12E, the optical fibers 340 are coupled to a processing window or cooling plate 317 in the form of a matrix array with arbitrary or regular spacing between the optical fibers 340. Although FIG. 12E depicts five such optical fibers 340, fewer or more suitably more optical fibers 340 can be used in other embodiments. For example, in one exemplary embodiment, a matrix array of 30 × 10 optical fibers can be used. In the embodiment depicted, the diode laser bar (or collection of diode laser bars) is located in the base unit (not shown). The diode laser bar (or collection of diode laser bars) can also be housed in the handpiece. The use of the optical fiber 340 allows the bar to be placed anywhere in the handpiece 310 or outside the handpiece 310.

  As an application example of a diode laser bar for the purpose of creating a heat damage area in human skin epithelium, a diode laser bar assembly emitting a wavelength λ = 1.47 μm as shown in FIGS. Use in skin, pressing mode (ie, do not move assembly on skin during use), ex vivo, at room temperature. The diode bar assembly had a sapphire window, which was placed in contact with the skin and pulsed with a laser for about 10 ms. The treated skin was then sliced from the center of the laser treatment area to expose the stratum corneum, epithelium and dermis sections. The resulting thermally damaged channels were about 100 μm in diameter and 125-150 μm in depth at 10 mJ per channel treatment.

B. Handpiece with Speed Sensor According to one aspect of the invention, the device provides a light emitting assembly for applying light energy to a target area of the patient's skin and a speed of movement of the head portion across the target area of the patient's skin. A sensor for measuring and a circuit in communication with the sensor for controlling the light energy to create a process isolation point can be provided. The circuit can, for example, control the pulsed illumination of the light energy source based on the speed of movement of the head portion across the skin to create a processing isolated point. In another aspect, the circuit controls the movement of the energy source within the device based on the speed of movement of the head portion across the skin, and processes certain areas of the skin while not affecting other areas. An isolated point can be made.

  FIG. 15 is a bottom view of an embodiment of the invention that includes a speed sensor for measuring the speed of movement of a handpiece across a patient's skin. The embodiment of FIG. 15 can be used, for example, in the embodiment of FIG. 12A. That is, the handpiece 310 of FIG. 12A can include a housing 310, a diode laser bar 315 (or more than one diode laser bar as in FIG. 12C), and a plate 317. FIG. 15 is a bottom view of a handpiece equipped with speed sensors 350, 352 therein.

  Various types of speed sensors can be used to measure the speed of the handpiece relative to the skin surface. For example, the velocity sensor may be a capacitive imaging array combined with an optical mouse, laser mouse, wheel / optical encoder, or flow algorithm similar to that used in optical mice. Capacitive imaging arrays can be used for both handpiece speed measurement and processing area imaging. Capacitive imaging arrays are often used for thumb fingerprint authentication for security purposes. However, capacitive imaging arrays can also be used to measure handpiece speed across the skin surface. By acquiring a volumetric image of the skin surface at a relatively fast frame rate (eg, 100-2000 frames per second), the flow algorithm can be used to track a specific shape in the image and calculate the velocity .

  In the embodiment of FIG. 15, two rows of capacitive imaging arrays 350, 352 are arranged, one on each side of the processing window 354, at the bottom of the handpiece. The output of the diode laser bar 356 is directed in the direction passing through the processing window, that is, the direction passing through the cooling plate or the like. The orientation of capacitive imaging arrays 350, 352 may vary depending on the various aspects of the invention. As the device is moved, both capacitive imaging arrays 350, 352 measure the speed of the handpiece across the patient's skin. This configuration can include circuitry that communicates with the capacitive imaging arrays 350, 352 to measure the velocity and determines an appropriate firing rate of the light source (eg, a diode laser) based on the velocity. Therefore, the circuit can also communicate with the laser and send pulses to the laser at an appropriate rate. A speed sensor incorporated in the handpiece can therefore send feedback to the laser pulse generator. In some embodiments, after the first pulse of radiation, the diode laser bar 356 cannot generate a pulse until the capacitive imaging array 350, 352 senses movement of the handpiece on the skin. This circuit can be placed in the handpiece in some aspects, but can be placed in the base unit in other aspects. If the diode laser bar 356 can be fired by the user (eg, by pressing a foot switch), the laser pulse generator for that laser fires a laser at a speed proportional to the speed of the handpiece.

  In operation, the above embodiment is used to move a handpiece with a single diode laser bar (or multiple diode laser bars) by hand across the skin surface at a speed proportional to the speed of the handpiece. By firing the laser, a uniform matrix of processing isolated points can be created. For example, by reducing the interval between laser pulses while increasing the speed of the handpiece, the treatment isolated points on the skin can be maintained in a constant linear matrix. Similarly, the treatment isolated points on the skin can be kept in a constant linear matrix by increasing the laser pulse interval while slowing the handpiece. The processing head with the processing window or light aperture of the handpiece can be rotated and the spacing of processing isolation points in the direction orthogonal to the movement of the handpiece can be varied.

  In addition to measuring the speed of the handpiece, the capacitive imaging arrays 350, 352 can also image the skin after creating a process isolation point and visualize the result of the process. Acquired images can be viewed in real time during processing. The handpiece can comprise a display showing the treated area of the skin under the cooling plate, for example. Alternatively, the acquired image can be stored in a computer and can be viewed after the processing is completed. In some aspects, the system can be configured to display images from both sensors so that the handpiece can be moved forward and backward.

  In the above configuration, a diode laser is used with a relatively low repetition rate because the laser is cut between processing isolation points. In some aspects of the invention, the diode laser can be used more efficiently by keeping the diode laser lit for a longer period of time, for example when the process isolation point is linear rather than a spot. FIG. 16 depicts an example of a handpiece 310 that can attach a diode laser bar 315 to a small linear translator 372 in the handpiece. The handpiece 310 of FIG. 16 may be almost the same as the above correspondence. That is, it can comprise a diode laser bar 315 in the handpiece proximate to the plate 317. However, this embodiment also includes a small linear translator 372 that can move the diode laser bar 315 forward or backward within the handpiece. Instead of the small linear translator 372, other suitable motors can be used such as, for example, a piezoelectric motor or any type of linear motor. In another aspect, the diode laser bar 315 can be attached to a cylindrical shaft that can be rotated to perform the same function as the linear translator 372. A single-axis galvanometer drive mirror can also be used.

  In the embodiment of FIG. 16, as the handpiece 310 is advanced (left in the figure), the diode laser bar 315 will move backward (right in the figure) through the handpiece at the same speed. When the diode laser bar 315 reaches the end of the handpiece 310, it will move toward the front of the handpiece and repeat this cycle. The interval between the lines of the processing isolated points can be adjusted by changing the time required for the movement of the handpiece from the last part to the front part. In this embodiment, for example, the speed sensor can measure the speed of movement of the handpiece 310 across the skin. This speed sensor may be similar to that described above. Such a speed sensor may communicate with a circuit (by motor 372) that moves the diode laser bar 315 based on the speed of the handpiece 310 across the skin. By appropriately moving the diode laser bar 315 in the handpiece 310 in this way, a matrix of treated isolated points can be created on the patient's skin.

  41A and 41B depict another inventive embodiment that includes a speed sensor. In this aspect, handpiece 400 includes a non-interfering EMR source 404 disposed within housing 402 of handpiece 400. The non-interfering EMR source 404 may be any of the above types including, for example, a linear flash lamp, an arc lamp, an incandescent lamp, or a halogen lamp. In one embodiment, the light source 404 is a Xe filled linear flash lamp.

  The handpiece 400 can also include an optical reflector 406, one or more optical fibers 408, and a light duct 410 (or concentrator). The optical reflector 530 plays a role of reflecting light and directing it toward the light collector 410. The concentrator 410 can be made of glass BK7 and can have a trapezoidal shape. In another aspect, the concentrator 410 can be made from a different material and its shape can vary. The concentrator 410 can be used, for example, to homogenize the beam. In some embodiments, the optical fiber 408 may not be used. When used, filter 408 can be used to exclude light of a specific wavelength from EMR source 404. In addition, in some embodiments, the optical reflector 406 may not be used. In some embodiments, a cooling plate (not shown in FIGS. 41A and 41B) can be attached to the housing 402 or the end of the light path to cool the patient's skin.

  The housing 402 can be equipped with a speed sensor 412. The speed sensor C560 can measure the speed of movement of the housing 402 relative to the patient's skin. In the embodiment of FIGS. 41A and 41B, the housing 402 of the handpiece 400 can move independently of the light source 404 in the housing 402. That is, when the housing 402 moves at a velocity V relative to the patient's skin, the light source 404 can move through the housing 402 so that the light source 404 remains fixed relative to the patient's skin. That is, the velocity v of the light source 404 relative to the patient's skin is approximately zero, which means that the light source 404 moves relative to the housing at a velocity −V within the housing. In this aspect, during the radiation action, the light source 404 remains stationary without moving, and the desired energy is reliably irradiated. When processing of the selected skin area is complete, the light source 404 can move within the housing 402 to reach its initial position. That is, the light source 404 can be advanced at alternating speeds v> V to process the next skin site (where v and V are both measured against the patient's skin). This alternating motion is depicted in FIG. 41B.

  As described above, the housing 402 includes the speed sensor 412 in order to synchronize the speed V of the housing 402 and the speed v of the light source 404. The speed sensor 412 can measure the movement of the housing 402 relative to the patient's skin, and then the light source 404 within the housing 540210 can be moved at an appropriate speed to remain fixed with respect to the patient's skin. The handpiece 400 or a base unit coupled to the handpiece may include circuitry that receives the housing speed of operation and sends a signal to the motor to move the light source 404 in the housing 402 at an appropriate speed. To that end, the handpiece 400 can include a linear motor or linear translator as described above to move the light source 404 within the housing 402.

  The above description indicates that the light source 404 can move within the housing 402. In some embodiments, the reflector 406, the filter 408, and the concentrator 412 can be coupled to a light source such that, when used, these components move within the housing along with the light source 404. FIG. 41B depicts the manner in which these components move with the light source 404.

In some embodiments using Xe filled linear flashlamp, spectral range EMR is 300～3000Nm, energy exposure to 1000 J / cm ^2, the pulse period is 0.1Ms～10s, and filling rate of about 1 % To 90%.

  Another aspect of the invention involves the use of imaging optics to image the patient's skin and use that information to determine drug application rates, EMR applications, etc., and optimize efficacy. For example, some medical or cosmetic skin treatments require accurate measurement of drug application rates and analysis of their effects in real time. The skin surface imaging system can detect the size of reversible or irreversible pores created using the techniques presented herein for creating treated isolated points in the stratum corneum. For this purpose, capacitive imaging arrays can be used in combination with imaging enhanced lotions and specially optimized navigation / image processing algorithms to measure and optimize application speed.

  The use of capacitive imaging arrays has been described above in connection with FIG. Such a capacitive imaging array can be used, for example, in the applicator 282 of FIG. 40 according to this aspect of the invention. As described above, in addition to measuring the speed of the handpiece, capacitive imaging arrays 350, 352 (FIG. 15) can also image the skin. The acquired image can be viewed in real time during processing through the display window of the device.

  An example of a capacitive sensor suitable for this aspect of the invention is a sensor having an array of eight image sensing rows x 212 image sensing columns. Due to the inherent limitations of capacitive array technology, a typical capacitive array sensor can process approximately 2000 images per second. In order to be able to process skin images in real time, the orientation of the sensor can be selected to aid functionality. In one aspect, for example, images are acquired and processed along columns. This makes it possible to accurately measure speeds up to about 200 mm / s.

  To make the sensor work with high reliability and accuracy, the surface of the skin can be treated with a suitable lotion. The choice of lotion is important for light-based skin treatment and navigation sensor operation. The lotion must be optically transparent to the selected wavelength, function as a lubricant to provide improved sensor image quality and reduce friction.

  A circuit including a processing algorithm or the like can be connected to the capacitive image sensor. Capacitive sensors and their associated processing algorithms can determine the type of lotion and its effect on the skin surface. This can be done in real time by continuously analyzing the spectral characteristics of the image. The processing algorithm can also process and control skin surface images using sensor calibration, image contrast enhancement and filtering, and navigation codes to support various applications.

  Images acquired in real time can be used for statistical analysis of marker concentration in the lotion. The marker may be the chromophore itself (ie, the chromophore that generates heat by the action of radiation) or a chemical that indicates the presence of the chromophore or drug in the lotion. In one example, the marker emits or reflects light in proportion to the incident light to indicate the concentration of chromophore or drug in the lotion. In this way, the capacitive sensor functions and can determine whether the marker concentration of a lotion is at an appropriate level. For example, the circuit can send a signal of the concentration of the marker to the user. Alternatively, the circuit can determine for a particular marker whether the marker concentration has reached a pre-selected set point concentration level. If the set point is not reached, the circuit can inform the user that more (or perhaps less) lotion is needed on the patient's skin. A selectable marker with the correct lotion pH level can also be used as a means to perform a light-enhanced safety function for the human body.

  The sensor can also function as a contact sensor. Thereby, the immediate contact of the handpiece with the patient's skin can be determined in real time. Depending on the combination of hardware and software, this determination can be made within an image frame. The algorithm measures skin contact and navigation parameters (position, velocity and acceleration) along the x and y axes in real time. This increases the safety of light treatment on human skin by allowing control of the speed and quality of skin contact. The quality of contact will be a function of the type of lotion and the pressure applied to the processing equipment.

  Capacitive sensors along with image processing and custom lotions can be used to detect skin defects in real time and measure their size. Sensor resolution depends on pixel size, image processing and sub-pixel sampling.

  Capacitive sensors and image processing can determine whether the device is operating on a biological skin or another shaped surface. Under appropriate sampling conditions, the type of skin that the device is traversing can be derived. This is accomplished by comparing the processed image with a stored pattern or a set of calculated parameters. In addition, a combination of capacitive sensors and image pattern recognition, navigation algorithms and custom lotions can be used to determine the presence of skin hair and provide statistical information regarding hair density and size.

  Two types of lotions, a capacitive sensor combined with a calibrated skin permeability lotion and an image enhancement lotion, can determine the skin rejuvenation effect for a wide range of skins. This analysis can be performed in real time by treating the skin with two types of lotions and then moving the capacitive sensor over the skin area to be impressed. The real-time algorithm determines the effective area of the process and a multiplication factor that exceeds the standard.

C. Perforated Mirrors FIGS. 7 and 8 depict an embodiment of the invention that generally creates process isolation points by using mirrors that are perforated or have other passage sites. The light passes through a hole in the mirror and strikes the patient's skin, creating a treatment isolation point. The light reflected by the mirror stays in the optical system and is again returned to the mirror by the reflection system so that the light can pass through the hole. In this way, the use of a perforated mirror is more efficient than using a perforated mask, where the mask absorbs light rather than reflecting light.

  In the embodiment of FIG. 7, patterned optical radiation that forms a processing isolated point is produced by a specially designed laser system 420 and output mirror 422. The laser system 420 and output mirror 422 can be housed in a handpiece, for example. In another aspect, the laser system 420 can be housed in a base unit, and light passing through the aperture in the mirror can be routed through an interference fiber optical cable to the handpiece aperture. In yet another aspect, a laser can be mounted in the handpiece and the microbeam from the laser can be directed to the skin using an optical system. In the illustrated embodiment, the laser system 420 includes a pumping source 426 that engineeringly or electrically excites the amplification medium 428 or the active laser medium. The amplification medium 428 is in the laser cavity defined by the rear mirror 430 and the output mirror 422. In this embodiment, any type of EMR source including interfering and non-interfering light sources can be used in place of the specific laser system 420 shown in FIG.

  According to one aspect of the invention, the output mirror 422 includes a strongly reflective portion 432 that provides feedback (or reflection) within the laser cavity. The output mirror 422 also includes a highly transmissive portion 434 that serves to create a plurality of light beams that illuminate the surface 438 of the patient's skin 440. Although FIG. 7 depicts the highly transmissive portion 434 as a circle, other shapes can be used including, for example, a square, a line, or an ellipse. The transmissive portion 434 is a hole in the mirror 422 in some embodiments. As another example, the transmissive portion 434 may be a partially transparent micromirror, an uncoated opening, or an opening in a mirror 422 with an anti-reflective coating. In these embodiments, the other part of output mirror 422 is a solid mirror or an uncoated surface.

  In one embodiment, the output mirror 422 functions as a diffractive sieve mirror having multiple spots. Such an output mirror 422 can also act as a distal or contact component of the optical system 420 against the surface 438 of the skin 440. In another aspect, the output mirror 422 can be made from a reflective material.

  Due to the high reflectivity of the exemplary skin tissue 440, the beam divergence decreases when it couples with the skin 440. In another aspect, one or more optical elements (not shown) may be added to the mirror 422 to project the screen pattern of the output mirror 422 onto the surface of the skin 440. In this latter example, the output mirror 422 is typically kept away from the skin surface 438 a distance defined by the imaging optical element.

  The length of the laser cavity L, the operating wavelength λ of the source 426, the gain g of the laser medium 428, the size or diameter of the transmissive part 434 of the output mirror 422 (ie circular), and the output coupler (if used) Appropriate selection helps to produce an output beam 436 with optimal characteristics for the creation of process isolated points. For example, when D2 / 4λL <1, the effective output beam diameter is much smaller than D and the size is close to the operating wavelength λ of the system. Using this method, any type of processing isolated point can be created.

Generally, the operating wavelength is in the range of about 0.29 μm to 100 μm, and the incident fluence is in the range of 1 mJ / cm ^{2 to} 100 J / cm ² . The effective heating pulse width is less than 100 times the thermal relaxation time of the patterned compound (eg, 100 fsec to 1 sec).

  In another embodiment, no chromophore layer is used. Instead, select the wavelength of the light and create the optical path directly.

  In one example, the spectrum of light is within or around the absorption peak of water. Such wavelengths include, for example, any wavelength of 970 nm, 1200 nm, 1470 nm, 1900 nm, 2940 nm and / or> 1800 nm. In another example, the spectrum is a lipid absorption peak such as 0.92 μm, 1.2 μm, 1.7 μm, and / or 2.3 μm, and wavelengths greater than 3.4 μm, or other intrinsic color developed within a protein or SC such as keratin It is close to the absorption peak of the group.

The wavelength can also be selected from a range in which this absorption coefficient is higher than 1 cm ⁻¹ , for example higher than about 10 cm ⁻¹ . In general, the wavelength is in the range of about 0.29 μm to 100 μm and the incident fluence is in the range of 1 mJ / cm ^{2 to} 1000 J / cm ² . The effective heating pulse width is preferably less than 100 times the thermal relaxation time of the target chromophore (eg, 100 fsec to 1 sec).

  Using the embodiment of FIG. 7, a processing isolated point can be created in the stratum corneum. Control of the stratum corneum permeability can also be achieved by absorption, scattering or refractive coupling. By cooling the skin or topical area, SC damage between pathways can be prevented and its size can be controlled.

  FIG. 8 depicts a second embodiment of a handpiece 450 that uses a mirror to reflect a portion of the EMR, while allowing a particular pattern of EMR to pass through the hole to create a process isolation point. The embodiment of FIG. 8 includes a light source 452 and some embodiments also include a beam shaping optics 454 and a waveguide 456. These components can be housed in a handpiece 450, such as the handpiece described above. In another embodiment, the light source 452 can be housed in a base unit that is outside the handpiece 450. The light source 452 may be a laser, flash lamp, halogen lamp, LED or other interference light source or heat source. In short, the light source 452 may be any type of EMR source described above. The beam shaping optics 454 may be reflective or refractive and can have the EMR facing down towards the output of the handpiece. The beam shaping optical system 454 can generally be placed above or to the side of the light source 452. The waveguide 456 can be used, for example, to make the beam 458 uniform.

  The handpiece 150 of the embodiment of FIG. 8 can also include an output window 460 near the optical output of the handpiece 450. The output window 460 can generally be provided with an impermeable coating. The coating may be a reflective coating such as a multilayer dielectric coating. Such a dielectric coating can be selected to have high reflectivity across the spectral band defined by the EMR source 452. If a high reflectivity can be selected, such a dielectric coating will not absorb as much light as it causes its heat generation. In addition, the dielectric coated window can be cooled as necessary to remove heat from the skin. Such dielectric coatings can be made in place, or more suitably by vacuum deposition of multiple dielectric layers. In some aspects, the output window 460 can be made from a microlens grating that serves to provide a spatial modulation of power density to the grating of optical isolated points.

  The coating of the output window 460 can have a plurality of openings (or holes or transmissive portions) 462 that transform the output beam into a plurality of beamlets. The opening 464 can be provided with an anti-reflective coating or can be fitted with a Fresnel or refractive lens for shaping the angular beam. The opening 464 need not be circular as depicted in FIG. The shape of the opening 464 can be adjusted according to the state of the skin to be treated. For example, the opening 464 may be circular, slit, square, oval, line or indefinite. In some aspects, the shape of the opening 464 can be deformed on demand (adaptive) using electro-optic or thermo-optic effects, depending on the underlying skin condition.

  The apparatus includes a cooling means 466 that can actively contact cool the process area. As described above, the cooling means 466 may be a sapphire cooling plate cooled by a water manifold or the like incorporated in the handpiece, for example. In addition, other types of cooling means 466 as described above may be used.

  The device of the embodiment of FIG. 8 can also include a device for monitoring the temperature of the waveguide 456 and / or the patient's skin 470. Temperature monitoring can be performed using, for example, an optical device. In such an embodiment, the search window 474 can be directed to the output window 460 using an independent light source 472. The reflected light is then detected by detector 476. As a result of the temperature change, the refractive index of the layers in the multilayer dielectric coating (or mirror or output window 460) changes and the reflection coefficient of the coating also changes. In this way, the change in temperature can be known from the measurement of reflection. The section 478 of the output window 460 can be optically isolated from the skin to reduce background parasitic signals from the skin 470 while measuring the temperature of the output window 460. The light source 472 and detector 476 can be incorporated into the handpiece.

  In some embodiments, the opening 462 of the output window 460 can be coated with a phase material that changes its transparency as a result of an increase in temperature. That is, the transparency of the opening 462 decreases as the temperature increases. In this way, the skin 470 can be prevented from being heated by reducing the transparency of the opening 416 and blocking the beamlet 474.

  In operation, the output window 460 contacts the processing area 470 (ie, the patient's skin). Next, the light source 452 is activated to output radiation from the handpiece. The opening 462 of the output window 462 creates a treatment isolation point on the patient's skin 470.

  The device of FIG. 8 can be used in either a pushing mode or a sliding mode. The pressing mode is a mode in which the radiation source is operated while the apparatus is placed on the skin and the apparatus is stationary on the skin. In the sliding mode, the device can be moved over the skin while in contact with the skin. In the pressing mode, the temperature (and possibly the damage profile) that occurs in the skin is entirely determined by the geometry of the opening and the irradiation / cooling parameters. In the sliding mode, further control is possible by changing the scanning speed.

  The apparatus of FIG. 8 can be optically coated (ie, on the processing window 460) to spatially modulate the light. Some embodiments may use a technique similar to a gradient mirror, but this is a mirror that varies in transmission along its radius. Embodiments with multiple gradient mirrors may be beneficial in increasing light source parameters (as a result of photon recirculation) and system cooling capacity (very thin coating thickness).

  In some embodiments, a coating (such as a multilayer dielectric strong reflective coating with a transparent zone grating) can be applied directly to the contact cooling surface of the sapphire cooling block. In such an embodiment, the entire sapphire block can be used as a cooling region, but the region that receives the irradiation is limited by the region of the transparent zone. Such an embodiment is effective in protecting the upper skin layer when treating deep dermis or fat in combination with LOI treatment.

  In another embodiment using a laser source, the laser itself can have a non-uniform output. For example, in such an embodiment, the laser itself can be surrounded by a reflector, but the reflector can be a strong reflector. The reflector that surrounds the laser, and in particular the reflector that surrounds the output end of the laser, can have an area that is less reflective than other areas. That is, the reflector of such a mode does not have uniform reflectivity. These basins can increase the radiation output from the laser source in the discontinuous regions (and holes). Thus, the reflector or mirror surrounding the laser itself can produce spatially modulated light as output. As a result, the laser source can be stored in the handpiece, and as a result, the laser source output and the output from the handpiece can be brought close to each other. As a result, the handpiece can be operated close to the skin to create a process isolation point.

D. Skin Lifting Means Another embodiment of the invention is illustrated in FIG. 42A. In this embodiment, the handpiece houses two light emitting assemblies 520 arranged at an angle with respect to each other. Each light emitting assembly 520 includes a light source 501, beam shaping means 502, and an output window 503. The light source 501 may be the various EMR sources described above. The beam shaping means 502 is a device that reflects and focuses the EMR from the light source 501. The output window 503 may be a contact plate for the patient's skin, similar to the contact or cooling plate described above.

  Skin lifting means 508 is used to crease the skin in the treated skin region 505. The skin fishing means 508 may be a vacuum means, for example. The illumination parameters (wavelength spectrum, power, cooling, etc.) can be selected so that the EMR beamlet 506 creates sufficient illumination area only in one or more limited spatial zones 507 that the beamlet 506 traverses. In this way, the dimensions of the damage zone (or the region of process isolation points) can be controlled very accurately. The apparatus of FIG. 42A can house a mask 504 with a coating or a reflective surface in the output window 503, similar to the apparatus described above in connection with FIGS.

  In one aspect, the mask 504 of each assembly 520 can slide relative to the corresponding window 503. For example, referring to FIG. 42B, the mask 504 can move through the window 503 so that, for example, the mask rests briefly against the patient's skin when the handpiece is moved over the skin. To that end, the mask 504 can be slid through the handpiece in the manner described above at a speed proportional to the speed of the handpiece moving over the patient's skin. Thus, the mutual position of the beamlets 506 and, as a result, the regions of the overlapping beamlets 506 can be controlled more precisely and a treatment isolation point can be created on the patient's skin. After the mask 504 rests briefly on the patient's skin, the mask 504 alternates positions within the output window 503 to process another region of the patient's skin.

  Similar to the device of FIG. 8, the device of FIG. 42A can be used in either a pushing mode or a sliding mode.

  Another means is a vacuum chamber surrounding the processing area. That is, the degree of vacuum changes so as to surround the tip of the handpiece (ie, the place where it comes into contact with the patient's skin). Such means would be advantageous when increasing the density of process isolated points. The vacuum chamber can pull the skin to the side and keep it pulled during processing and can contact the tip. When the skin is released from the vacuum chamber, the skin returns to its original size with significantly dense isolated points.

  The use of a vacuum chamber surrounding such a handpiece tip also increases blood circulation, which may be advantageous for processing conditions where hemoglobin is the chromophore. By further increasing the vacuum force, the skin can be brought into direct contact with the handpiece tip, blood pressure within the contact area will be restored and blood circulation will be reduced. If the chamber design allows the skin to be pulled laterally outside the tip region, further squeezing the blood vessels will increase the skin's permeability to specific wavelengths of light and increase the light penetration depth. Let's go. Another advantage of this concept is that lower temperatures and lower energy levels can be used to pull and denature the skin. In addition, by pulling the skin, the light scattering level can be lowered and the penetrability can be increased.

E. Handpiece with non-interfering light source to create a processing isolated point FIG. 9A shows another aspect of the invention. In this aspect, the invention is an EMR source 542 and a handpiece 540 comprising a tip 544 shaped to spatially modulate and focus the output light, thereby forming a treatment isolated point on the patient's skin. The EMR source 542 is in some embodiments a non-interfering light source of any type described above, including, for example, a linear flash lamp, an arc lamp, an incandescent lamp, or a halogen lamp. In one embodiment, the light source 542 is a Xe filled linear flash lamp.

  The handpiece 540 can also include an optical reflector 546, one or more optical filters 548, and a light duct 550 (or collector). The optical reflector 546 plays a role of reflecting light toward the light collector 550. The concentrator 550 can be made from BK7 glass and has a trapezoidal shape. In another aspect, the concentrator can be made from a different material and can be reshaped. The concentrator can be used, for example, for beam homogenization. In some embodiments, the optical filter 548 is not used. When used, filter 548 serves to filter out certain wavelengths of light from EMR source 542. In addition, in some embodiments, the optical reflector 546 may not be used. In some embodiments, a cooling plate (not shown in FIGS. 9A-E) can be attached to the handpiece housing or light path end to cool the patient's skin.

  The tip 544 of the concentrator 550 can comprise an array shaped to spatially modulate and focus the output light, thereby creating isolated points on the patient's skin. For example, the tip 544 can be a pyramid (Fig. 9B), conical (Fig. 9C), hemisphere (Fig. 9D), groove (Fig. 9E) type prism, or an array of other structures suitable for spatial modulation and convergence of the output light Can be provided. To that end, the tip can be made from any type of array, such as a microprism, that modulates and converges the output to create an isolated point of processing.

In the exemplary embodiment using the Xe filled linear flash lamp of FIGS. 9A-E, the spectral range of electromagnetic radiation is about 300-3000 nm, the energy exposure is up to about 1000 J / cm ² and the laser pulse time is about 10 ps to 10 s. And the fill factor is about 1% to 90%.

  FIG. 43A shows another embodiment of the invention. In this aspect, the invention is a handpiece 540 that includes many of the same elements as the embodiment of FIG. 9A. That is, the embodiment of FIG. 43A can include a MER source 542, an optical reflector 546, one or more optical filters 548, a light duct 550 (or collector), and a cooling plate (not shown). Each of these elements may be similar to or the same as those described above with respect to FIG. 9A.

  In the embodiment of FIG. 43A, the tip 544 of the concentrator 550 can be finished as an optical diffusing surface with a clear (polished) spot to spatially modulate the output light. For example, referring to FIG. 43B showing the side and top surfaces of the tip 544, the tip 544 includes a scattering film 560 having a circular opening 570. A scattering film 560 with a circular opening 570 modulates the output to create a treatment isolation point on the patient's skin. Specifically, the opening 570 (which can be a clear, polished spot) allows the EMR to pass and creates a processing isolation point.

  FIG. 13A shows another embodiment of the invention. In this embodiment, the invention is a handpiece 540 comprising many identical elements of the embodiment of FIGS. 9A and 43A. That is, the embodiment of FIG. 13A can include a MER source 542, an optical reflector 546, one or more optical filters 548, a light duct 550 (or collector), and a cooling plate (not shown). Each of these elements may be similar to or the same as those described above with respect to FIG. 9A.

In the embodiment of FIG. 13A, the light guide 550 can be made from a bundle of optical fibers 580 doped with rare earth metal ions. For example, the light guide 550 can be made from a bundle of Er ³⁺ doped fibers. The active ions inside the light guide core 582 function as a fluorescent (or superfluorescent) conversion material, resulting in the desired spatial modulation and spectral conversion. In this way, the light guide 550 of the embodiment of FIG. 13A can create an EMR spatial modulation to create a processing isolated point.

  FIGS. 13B, 13C and 13D show an embodiment in which the optical fiber 580 covers the EMR source 542 to couple the light into the optical fiber 580. As FIG. 13C shows, each individual fiber, or group of fibers 580, can direct its output to the skin. FIG. 13D is a bottom view of the output of the handpiece. As FIG. 13D shows, the fiber 580 has a spatially modulated output distribution to create a processing isolated point.

  FIG. 13E shows another embodiment using the same overall structure as the embodiment of FIGS. 13A, 13B and 13C. In the embodiment of FIG. 13E, the output of the fiber bundle 580 (ie, the bundle of FIGS. 13B-D) has a tip made of an array 586 of microlenses attached to the output surface of the light guide. The array of microphone lenses 586 serves to converge and concentrate the output from the fiber bundle 580 to create an isolated point of damage.

  FIG. 11 shows another embodiment of the invention. In this aspect, the invention includes a handpiece 600 having a plurality of sets of EMR sources 604, reflectors 602, filters 606, and light guides 608. The output of each light guide may be a cooling plate. Each of these components may be similar to or the same as those described above with respect to FIG. 9A. In the body, the spacing between the individual EMR sources (emitters) can provide the desired spatial light modulation to shape the process isolation points. FIG. 11 shows four sets of EMR sources 604 and associated components. However, in other embodiments, more or less than four sets of EMR sources 604 can be used. In addition, in some embodiments, an array of EMR stools can be used. For example, such an array may be 4 × 6, for a total of 24 EMR sources.

F. Handpiece with Total Internal Reflection FIGS. 10A-10C illustrate another embodiment in which all of the output EMR from the handpiece is internally reflected when the handpiece is not in contact with the patient's skin. When the handpiece is in contact with the patient's skin, the output EMR is spatially modulated to create a treatment isolation point on the patient's skin.

  In the embodiment of FIGS. 10A-10C, the invention is a handpiece 540 with many of the same components as the embodiment of FIGS. That is, the embodiment of FIGS. 10A-10C can include an EMR source 542, an optical reflector 546, one or more optical filters 548, a light duct 550 (or collector), and a cooling plate (not shown). Each of these components may be similar to or the same as those described above with respect to FIG. 9A.

  The total internal reflection in the embodiment of FIGS. 10A to 10C depends on the shape of the tip 544 of the optical duct 550. The tip 550 is an array of prisms such as pyramids, hemispheres, cones, etc. as described in FIGS. 10B and 10C. The array of elements is dimensioned and shaped to totally reflect light (TIR) when the tip 544 is in contact with air as shown in FIG. 10B. In contrast, as shown in FIG. 10C, when the tip 544 is in contact with the lotion or skin surface, the tip 544 does not TIR (block TIR). Furthermore, when the tip 544 is in contact with the lotion or skin, the EMR is optically spatially modulated in the contact area of the patient's skin and concentrated to create a processing isolation point.

In the exemplary embodiment of FIGS. 10A-10C using a Xe filled linear flash lamp, the spectral range of electromagnetic radiation is about 300-3000 nm, the energy exposure is up to about 1000 J / cm ² and the laser pulse time is about 10 ms to 10 seconds. And the filling rate is about 1% to 90%.

  The embodiment of FIGS. 10A, 10B and 10C depicts the use of a non-interfering light source in the handpiece. However, the mechanism can also be used to generate TIR in an embodiment using an interfering light source such as a solid state laser or a diode laser bar. Referring to the embodiments of FIGS. 12A-E, 15 and 16, the light from the diode laser bar 315 (FIG. 12A) can also be coupled to the skin via a total internal reflection (TIR) prism. Since the diode laser bar 315 may not be placed in close proximity to the skin surface, an optical system that reprojects the emitter onto the skin may be required. Thus, the emitter may be reprojected onto the skin using a tip with a prism or the like. In one embodiment, a TIR prism can be used. When the TIR prism is not in contact with the patient's skin, the light from the diode laser bar will be internally reflected and no light will be emitted from the headpiece. However, when the patient's skin is covered with a lotion with the same refractive index and the skin comes into contact with the handpiece (particularly the prism), the light couples with the skin. In this manner, a TIR reflecting prism or array can be used in an embodiment that utilizes an interference light source in a manner similar to that described above for a non-interference light source. This shape may be important for eye and skin safety.

G. Solid State Laser Embodiments FIGS. 14A, 14B and 14C illustrate additional embodiments of the invention. FIG. 14A shows an embodiment where the apparatus includes a laser source 620, a focusing optical (eg, lens) 622, and a fiber bundle 624. Laser source 620 may be any source suitable for this application, such as a solid state laser, a fiber laser, a diode laser, or a dye laser. In one embodiment, the laser source 620 may be an active rod made of garnet doped with rare earth metal ions. The laser source 620 can be housed in a handpiece or a separate base unit.

  In the exemplary embodiment of FIG. 14A, the laser source 620 is surrounded by a reflector 626 (which can be a strong reflector HR) and an output coupler 628. In another aspect, reflector 626 and coupler 628 are not required. Various types and geometries of reflectors 626 can be used. The fiber bundle 624 is optically disposed downstream of the lens, so that the optical lens 622 focuses light onto the fiber bundle 624 and converges.

  In one embodiment, in order to focus the EMR on the patient's skin 632, an optical element 630, such as a lens array, is used to direct and output the EMR from the fiber bundle 624. The optical element 630 may be any element (such as a lens or microlens) or an array of elements suitable for converging EMR. In the embodiment of FIG. 14A, the optical element 630 is a microlens array. In another aspect, the optical element 630 may not be used. In such an embodiment, the output from the fibers in the fiber bundle 624 is tied to one side of the processing window (such as the cooling plate of the device) and the patient's skin 632 is tied to the opposite side of the processing window.

  In operation, the laser source 620 creates an EMR, and the reflector 626 reflects a portion of it toward the output coupler 628. The EMR then passes through the output coupler 628 to the optical lens 622, where the lens converges toward the fiber bundle 624. A microlens array 630 at the end of the fiber bundle 624 focuses the EMR onto the patient's skin 632.

  FIG. 14B shows another embodiment of the invention. In this embodiment, the apparatus comprises a laser source 620 and a phase mask 640. The laser source 620 can be any type of laser source and can be housed in the handpiece or in a separate base unit, similar to the embodiment of FIG. 14A. In one embodiment, the laser source 620 may be an active rod made of garnet doped with rare earth ions. Similarly to the embodiment of FIG. 14A, the laser source 620 can be surrounded by a reflector 626 (which may be a strong reflector HR), and the EMR can be output into the output coupler 628 (OC).

  The embodiment of the invention of FIG. 14B includes a phase mask 640 disposed between the output coupler 628 and the optical element 642. The phase mask 640 can comprise a set of apertures that spatially modulate the EMR. Various types of phase masks can be used to spatially modulate the EMR to create treatment isolation points on the patient's skin 632. The optical element 642 may be any element (such as a lens or microlens) or an array of elements suitable for focusing EMR radiation onto the patient's skin 632. In the embodiment of FIG. 14B, the optical element 642 is a lens.

  In operation, the laser source 620 creates an EMR, and the reflector 626 reflects a portion of it toward the output coupler 628. The EMR then passes through the output coupler 628 to the phase mask 640, where the phase mask spatially modulates the radiation. An optical element 642 optically downstream of the phase mask 640 and receiving the output EMR from the phase mask 640 creates an image of the aperture on the patient's skin.

  FIG. 14C shows another embodiment of the invention. In this embodiment, the apparatus comprises a plurality of laser sources 650 and optics that focus the EMR onto the patient's skin 632. The plurality of laser sources 650 may be any source suitable for this application, such as a diode laser or a fiber laser. For example, the laser source 650 may be a bundle of active rods made of garnet doped with rare earth ions. The laser source 650 may be surrounded by a reflector and / or output coupler as needed, similar to the embodiment of FIGS. 14A and 14B.

  In the embodiment of FIG. 14C, the optical element 642 can be used to focus the EMR on the patient's skin 632. Corresponding elements (such as lenses or microlenses) and arrays of elements can be used for the optical element 642. The optical element may be a lens 642, for example.

  In operation, the laser bundle 650 creates an EMR. The EMR is spatially modulated by spatially separating the laser source 650 as shown in FIG. 14C. As a result, the EMR output from the laser source 650 is spatially modulated. The EMR passes through the output coupler 628 to the optical element 642, which converges the EMR onto the patient's skin 632 to create a process isolation point.

In the exemplary embodiments of FIGS. 14A, 14B, and 14C, using garnet laser rods doped with rare earth ions, respectively, the spectrum of electromagnetic radiation is about 400-3000 nm and the energy exposure is up to about 1000 J / cm ² ; The laser pulse time is about 10 ps to 10 seconds, and the filling rate is about 1% to 90%.

H. Consumer-oriented products and methods In another aspect, the invention is highly permeable in SC without causing irreversible structural damage to the tissue or with minimal such damage. Includes creating many zones. Reversible permeability is achieved by creating local permeability in the SC for a limited time. In general, this limited time corresponds to the application of EMR energy. After applying EMR energy, the SC closes. Alternatively, permeability may be maintained for a period of time after applying EMR energy. By limiting the permeability time to a limited time, the risk of infection can be prevented. By using the principle of the present invention, such processing can be performed safely and painlessly. For example, it can be performed by a general person, that is, a person who has not received special training. One such use is aimed at improving the local delivery of cosmetics or pharmaceuticals when used at home.

  FIG. 44 is a schematic diagram of a handpiece 670 according to this aspect of the invention. In one example, the handpiece 670 irradiates the beamlet 674 with a pattern 672 that stimulates the surface 676 of the human skin 680. This creates a heat zone in the skin, eg, moderate hyperthermia, thereby creating a temporary permeation path 682. The transient permeation path 682 can be created by inducing a continuous phase transition in the intercellular lipid associated with the stratum corneum of the stratum corneum 684. The deer in the SC begins to dissolve at about 35 ° C and completely dissolves at about 85 ° C. The handpiece 670 can also include a vibrator and / or ultrasound device for massaging the skin, or iontophoresis to increase permeability.

  In one example, the handpiece 670 uses an internal array of waveguides or an array of light emitting diodes (LEDs) or laser diodes to create a beamlet pattern 672. Preferred LEDs or laser diodes have already been described in connection with other embodiments. For example, a one-dimensional array of diode lasers or a stack of light emitting diode bars can be used. Numerous other types of EMR sources can also be used in this embodiment. In some aspects, the handpiece 670 can include multiple light sources for locally photoactivating the inside of the skin. In some embodiments, the wavelength of light is selected to make the SC transparent for a period of time while not damaging the skin.

  For controlled heating of the SC, endogenous or exogenous chromophores can be used. For endogenous chromophores, water, lipids or proteins can be used. In one example, the light spectrum is within or around the absorption peak of water. Such wavelengths include, for example, any wavelength of 970 nm, 1200 nm, 1470 nm, 1900 nm, 2940 nm and / or> 1800 nm. In another example, the spectrum is a lipid absorption peak such as 0.92 μm, 1.2 μm, 1.7 μm, and / or 2.3 μm, and wavelengths greater than 3.4 μm, or other intrinsic color developed within a protein or SC such as keratin It is close to the absorption peak of the group.

  As a result of the phase transition, the equilibrium between the lipid solid phase and the liquid layer shifts to the liquid layer side. That in turn generates a highly permeable passage (not drawn) through the SC. A molecule, molecular complex or particle 694 of the topical composition is released from the applicator 688 of the handpiece 670 or applied directly to the skin and penetrates the epithelium and dermis through pathway 682 by enhanced diffusivity. . The topical composition can be applied to the skin before, during, or after EMR treatment depending on the time during which SC permeability is increased.

  In some embodiments, the bottom plate 690 of the handpiece 670 is cooled to increase skin safety and comfort while accelerating the return of the SC to normal permeability after composition delivery. In another aspect, the plate 690 is heated to facilitate the path creation process. After treatment, additional topical compounds can be used to accelerate healing of the treated SC.

  In some embodiments, the order of heating can be reversed. For example, the handpiece 670 can create a hypothermic zone on the skin surface 676 to initiate a “clotting” process on lipids in the SC. As a result, the lipid component contracts to create a pathway with enhanced permeability. The above form is maintained at the minimum allowable temperature even when the basement membrane temperature is about 15-18 ° C. In such an embodiment, the plate can be heated for the purpose of better skin protection and rapid permeability recovery.

  This concept can also be used to transiently deliver cosmetic compounds into the skin, preferably into the epithelium. The compound is removed from the skin by epithelial growth. In addition to this, the compounds can also be used for whitening or tanning the skin, improving light diffusivity and tattooing.

Heat transmission of stratum corneum The lattice of heat isolation points can be used to increase the permeability of the stratum corneum to various degrees in various ways, depending on the invention.

  In the temperature range of 35-40 ° C., the outermost layer of the skin is exposed to “mild hyperthermia” which is sufficient to enhance the diffusion of some compounds into the stratum corneum and the clear layer. Permeability increases with “moderate hyperthermia” in the range of 40-50 ° C. These temperatures are sufficient to initiate a phase change that partially lyses the stratum corneum and the clear crystalline lipid intracellular matrix that appears to be transparent. In general, however, changes induced by this moderate heating are reversible. When the heat source is removed, the lipid cell matrix recrystallizes with little or no permanent change. At temperatures in the range of 50-100 ° C., the skin is exposed to “strong hyperthermia” that causes changes in the stratum corneum and clear layer structures that are only partially reversible. The lipid intracellular matrix is completely liquefied by 85 ° C. When the stratum corneum is heated to a temperature of 100 to 200 ° C., water evaporates and induces irreversible destruction in the stratum corneum, creating a fine gap, but does not remove the stratum corneum. Rapid heating of the stratum corneum to temperatures in excess of 200 ° C. causes denaturation of stratum corneum proteins and evaporation of stratum corneum lipids or water. Holes are created in the stratum corneum by the pressure waves resulting from the evaporation.

  Moderate and intense hyperthermia generally induces a pain response in the subject. In general, sensory nerves in the nipple dermis serve to sense and transmit heat, pain and other unpleasant sensations. When exposed to temperatures above 40-43 ° C., these sensory nerves transmit pain responses in most subjects. Thus, at least local anesthesia is often required when moderate and intense hyperthermia is applied uniformly or continuously to the skin surface. Local anesthesia can be achieved, for example, by using a topical pharmaceutical (eg, lidocaine, LMX4 ™, Ferndale laboratories, Inc., Ferndale, MI) or by pre-cooling the treated area to reduce skin sensitivity.

1. EMR Absorbing Particles In some embodiments, the invention provides a film having a grid of dots, lines or other shapes of EMR absorbing particles embedded in or within the film. The arrangement of the EMR absorbing particles may be random or may have a regular pattern such as a grid structure. For example, the material of the film may be a soft composition that is transparent, thermally stable, and preferably has low thermal conductivity, such as an optically clear polymer; whereas the material of the EMR absorbing particles is EMR A material such as carbon, ink or metal suitable for the source. EMR absorbing particles may be spheres having a diameter of 1-1000 μm, generally 50-500 μm. The spheres can be embedded in the film with a fill factor of about 1-100%. At high filling rates, such as about 50-100%, the film also serves to protect the skin from light. The size of the thermal isolated point on the skin is the temperature of the particle, the strength of the skin-particle contact, and the particle / skin interface and releases the heat of the particle bound to the particle / skin interface, Or it will be smaller or larger than the EMR absorbing particles depending on the presence of other materials with suitable thermal properties (eg, oils, lotions, petrolatum) to help retain.

  In some embodiments, the film can include additional wave guides on top of the EMR absorbing particles. In some embodiments, the waveguide is conical. The purpose of the waveguide is to further concentrate EMR energy at isolated points. This can be achieved, for example, by using a transparent material having a higher refractive index than the film and by utilizing the total internal reflection (TR) phenomenon.

  In another aspect of the invention, the film or EMR absorbent particles of the film can be impregnated with cosmetics or pharmaceuticals and delivered throughout the stratum corneum. In these embodiments, the EMR-absorbing particle includes a cavity filled with the agent to be delivered and has an opening directed toward the skin surface. First, the opening is closed with a plug to prevent leakage of the active substance. When EMR energy is applied, the EMR absorbing particles are heated, resulting in a thermally isolated point with increased permeability to the skin. The material of the plug is selected so that it can dissolve with increasing temperature and release the agent to the thermal isolation point. In addition, in some embodiments, the particulate inclusions can expand to create a jet-like continuous flow toward the skin.

  In one specific embodiment, a film with a pattern of carbon dots is used. The carbon dots can be embedded in the film, or can be transferred from the film to the skin to remove the film. For example, the carbon dots can be transferred with a first pulse laser, and then the dots on the skin can be irradiated with a second pulse laser, or irradiated from another light source.

  In some embodiments, a large amount of EMR absorbing particles is exposed to the EMR in the form of a uniform incident optical beam. Such a beam can be produced, for example, by a laser or a flash lamp. The exposed particles absorb radiation and release it as heat into the underlying stratum corneum region, increasing the permeability of the stratum corneum and creating a more permeable pathway for drug delivery.

  The wavelength of EMR used to expose EMR absorbing particles may be important. For example, the wavelength will be in the range of about 290 nm to about 1000 μm. Generally, the wavelength is weakly absorbed by the body part, particularly the skin, but is well absorbed by the EMR absorbing particles. The ratio of the absorption coefficient of EMR absorbing particles to the absorption coefficient of skin must be greater than 1. Thus, upon irradiation, the EMR absorbing particles are heated exclusively, transferring heat to the underlying stratum corneum of the skin. In contrast, EMR that does not hit the particles is not efficiently absorbed by the skin, and the generated heat is widely distributed in the depth direction within the skin, so the heat diffuses and the skin or other structures Avoid adequate local heating and damage to objects.

In some embodiments, the incident fluence ranges from 1 mJ / cm ^{2 to} 1000 J / cm ² . Assuming that highly absorbent particles are used, 1 mJ / cm ² is generally required every time the stratum corneum is heated at 20 ° C.

  In some embodiments, incident radiation is used in a pulsed manner to minimize damage to the epithelium and dermis. The effective heating pulse width must be less than 100 times the thermal relaxation time of the isolated point. Thus, typically the pulse width is in the range of 100 fetoseconds to 1 second depending on the size of the isolated point selected.

  In addition to the use of a film as described above, the invention can be practiced by providing a topical composition comprising EMR absorbing particles (eg, chromophores) in a lipid carrier, such as a solution, suspension, cream or lotion. The topical composition can be applied to the skin to randomly distribute EMR absorbing particles on the surface. The density on the surface of the EMR absorbing particles can be controlled by changing the concentration of EMR absorbing particles in the topical composition or by changing the amount of topical composition applied. By actuating the EMR source, the EMR absorbing particles are warmed, resulting in the selective generation of thermal isolation points in the process. Any of the various materials described above for EMR absorbing particles can be used for the topical composition.

  In another embodiment, a spatial selection pattern of EMR treated isolated points can be created by applying a desired pattern of topical composition containing exclusively exogenous exogenous chromophores to the skin surface. First, a desired pattern of the composition is drawn on a selected skin treatment area using a print head mounted on a scanner. The EMR delivery system then delivers a beam of radiation to the treatment area, thereby preferentially heating the composition. The generated heat diffuses from the chromophore of the patterned composition, resulting in a corresponding pattern of hot isolated points. The dimensions of the thermal isolated points are, for example, between 1 μm and 3 mm, and the distance between the isolated points is, for example, 1-1000 times the dimensions.

In another embodiment, instead of applying the topical composition directly to the skin surface, the composition can first be applied to an EMR permeable film. The film can then be applied to the skin surface and radiation can be delivered through the film. The spectral composition of the incident radiation must match the absorption spectrum of the chromophore. In this embodiment, various substances including carbon, metal (eg, Au, Ag, Fe), organic dye (eg, methylene blue, toluidine blue, trypan blue), non-organic dye, and fullerene can be used as the chromophore. However, it is not limited to these. The fluence of radiation may be in the range of 0.1 to 1000 J / cm ² , for example, and the pulse width may be in the range of 1 ps to 10 seconds, for example. The desired pattern may not be regular or predetermined. It depends on the skin condition of the desired treatment area, or may be made on the fly by a doctor or technician.

  In another aspect, all the features described with respect to the film can be performed at the tip of the light source in contact with the skin.

  In another aspect, the EMR source headpiece can be scanned along the skin surface. A handpiece tracking / imaging device (eg, a digital camera or capacitance array) can find, segment and track the target volume (eg, pigmentation disorder or vascular abnormality). The handpiece EMR absorbing particle (eg, chromophore) dispensing device can dispense the EMR absorbing particles following the projection of the target on the skin surface according to the tracking information. The EMR source can then irradiate the EMR absorbing particles distributed to the processing region.

  Another aspect is a dermatological delivery device that includes a substrate. According to this aspect, the substrate has a plurality of absorbent elements as described above, and includes the composition on at least one side of the substrate. Incident rays from the energy source heat the absorbing element, which creates a treatment isolated point in the human stratum corneum. After removing the substrate, at least an essential part of the composition remains on the human skin. That is, a composition that is a cosmetic, therapeutic or pharmaceutical agent is applied or formulated in or on the substrate such that when the substrate is removed, at least a significant portion of the composition remains on the skin.

  If the purpose of the treatment is to promote penetration of cosmetics or pharmaceuticals, the tracking / image or device can be replaced with an active substance separator.

2. Pyrogenous compound In another embodiment, a film containing particles of a pyrogenic compound is used, and the particles are held near or placed on the skin surface.

  In some embodiments, a small amount of exothermic compound 780 is bonded or embedded in film 782 or other carrier as shown in FIG. A film 782 is applied to the surface of the skin 784 and the compound is held in thermal conduction with the skin 784. In some embodiments, light or electric discharge (drawn from light source 788) is used to ignite (initiate) the reaction of the exothermic compound, which triggers the controlled release of chemical energy to the underlying stratum corneum. To do. For example, a mixture of a light absorbing chromophore (eg, carbon) and an exothermic reagent (eg, nitroglycerin) can be used. The chromophore absorbs energy and releases it as heat, which ignites the exothermic reagent.

3. Patterned radiation In another embodiment, a continuous or quasi-continuous coating of EMR absorbing compound is applied to the skin. For example, a thin layer of carbon paper, dye solution, or EMR absorbing lotion can be used. The EMR source must have a spectrum that matches the absorption peak of the EMR absorbing compound. For example, when water is used as the EMR absorbing compound, the spectrum may include wavelengths of about 1.45, 1.9 and> 2.3 μm.

  The continuous coating is then exposed to an EMR pattern. EMR patterns can be created using a uniform radiation source, such as a laser or flash lamp, and an amplitude or phase mask to create a pattern of optical isolated points or beamlets, or other delivery system. Alternatively, the beamlets can be made using multiple sources such as multiple diode laser emitters or fiber bundles. The beamlet locally heats the EMR absorbing compound (eg, chromophore) coating, which creates a thermal isolation point.

  In another aspect, an interference pattern (eg, a moire pattern) is created by a source on the skin. The pattern is designed such that the nodes or regions of constructive interference exceed the threshold to create a transmission path through the stratum corneum, while staying below the threshold between nodes.

  In a specific aspect, the patterned radiation is a periodic grating. The parameters of the patterned radiation are controlled by choosing the geometry of the incident beam, the source settings, the properties of the EMR absorbing compound and its concentration.

High Speed Acne Treatment Device Another embodiment of the invention is shown in FIGS. 49A-B and 51A-B. The purpose of the device of this embodiment is to quickly reduce the volume and redness of inflammatory acne damage (single injury treatment). For example, reduction of redness and inflammation will occur within about 8-12 hours. Although these aspects are written for acne treatment, other aspects can be used as well.

A. Acne Treatment Device Using High Power FIGS. 49A, 49B and 50 show one embodiment of an acne treatment device. In this aspect, the primary role of light 842 is to facilitate the delivery of topical drugs through the stratum corneum without significantly compromising the protective function of the skin. In some cases, light can also provide additional benefits for acne relief, apart from topical drugs. The body-like system comprises an applicator 840 that contains a light and a topical drug and delivers a batch 844 that generates heat and promotes penetration into the stratum corneum when exposed to light. This drug exerts vasoconstriction and anti-inflammatory action, and can reduce bacteria. This may be a medicine with a PDT effect.

  In the main body, the device is a pulsed light system that functions as a hand-held cordless applicator 840 and charger 850. In this aspect, applicator 840 is a self-supporting device. In another aspect, the applicator 840 can be attached to the base unit by a connecting cord. Applicator 840 includes a rechargeable battery 846 that stores sufficient energy for a plurality of optical pulses, eg, up to 15 optical pulses. A charger contact plate 852 on the applicator 840 engages the charger 850 to recharge the rechargeable battery 846 (see FIG. 49B). The applicator 840 can also include a power source 854.

  The applicator 840 can also include a spring and contact plate that together form a springed contact plate. The spring contact plate can reliably control the mechanical pressure of the contact plate 858 on the patient's skin 860. In addition, the spring contact plate can also output light from the applicator 840 only when the plate is in contact with the patient's skin 860. For example, a sensor or the like may be provided in the applicator 840 to sense that the contact plate 858 is in contact with the skin 860, and the applicator may be used when the contact plate 858 is not in contact with the patient's skin 860. You can also turn off the light source. The contact plate 858 can be made of a transparent material such as sapphire. The contact plate may also have other characteristics similar to other contact plates described herein (eg, cooling characteristics).

  In the embodiment of FIGS. 49A, 49B, and 50B, the applicator 864 includes an EMR source 862, and optionally a reflector 864 and a filter 866. Applicator 864 and, if used, filter 866 may be the same or similar to those described in the above embodiments. The EMR source 862 is a device based on a Xe flash lamp, for example, as shown in FIG. 49A. In other embodiments, other EMR sources 862 can be used. The applicator 840 can also include a controller 868 that controls the light fluence, the filtering of light through the filter 866, and other functions.

  The system also includes a patch 844. The role of patch 844 is dual. The first serves as a container for the topical composition 870 for use through the skin. Second, it can model highly absorbing optical patterns as a collection of stitches or isolated “isolated points” (such as dots). FIG. 50 shows an enlarged patch 844 (applicator 840 is not the same size in FIG. 50). Referring to FIG. 50, the patch 844 includes a topical pharmaceutical product 870, an adhesive ring 874, an exothermic adhesive film 876, a light absorber pattern 872, and a protective film 878. Topical drug 870 may be any compound, composition, or pharmaceutical intended to be delivered through skin 860. For example, it may be a compound that treats acne.

  The pattern of light absorber 872 can be made from inert and biocompatible materials, ensuring high absorption of light energy. For example, the light absorber can be made from carbon powder. Various types of light absorbers 872 can be used in place of or in addition to the carbon powder. The pattern of light absorber 872 may vary in different embodiments. In some embodiments, an organized matrix arrangement can be used, while in other embodiments, a low or random arrangement of light absorbers 872 can be used.

  An adhesive ring 874 is formed on the bottom of the patch 180 and is used to affix the patch 844 to the skin 860. Adhesive ring 874 can be shaped as a ring with an open center, but can take other shapes. The opening prevents the adhesive ring 874 from interfering with the operation of the patch 844. That is, the opening contacts the skin 860 but does not contact the adhesive ring 874, so that the function of the patch 844 is prevented from being obstructed by the adhesive ring 874. The adhesive ring 874 can be made from any adhesive material. In addition, although the term adhesive ring is used herein, any tool for bonding the patch 844 to the skin surface 860 can be used in place of the adhesive ring. The protective film 878 covers the bottom of the patch 844 before use, and is removed before use. The protective film 878 serves to keep the adhesive ring 874 fresh until use and to protect the other parts of the patch 180 from contamination. The occlusive film 876 is generally transparent to the light 880 and serves to protect the top of the patch 844.

  In operation, the patch 844 comes into contact with the top of the skin. In one embodiment of acne treatment, the patch 844 can be placed over a skin portion 860 with acne damage 861. The user can then send a pulse of light 880 to patch 844 using applicator 840. When a pulse of light 880 irradiates the patch 844, the light absorber 872 absorbs the light energy, resulting in a rapid temperature rise. Because the light absorber 872 is in contact with the skin surface 860, some of the thermal energy is transferred to the stratum corneum, creating a corresponding pattern of channels with increased permeability in the stratum corneum. As a result, the penetration of the topical medicine 870 into the skin 860 is accelerated, thereby enabling faster drug effects. The patch 844 is then peeled off the skin 860 for a short time, for example, about 2 hours. The parameters of the light / patch system are chosen so that no irreversible damage occurs to the stratum corneum; i.e. the integrity of the skin barrier is preserved for a short time. The benefit of being a substrate is a quicker appearance improvement in acne damage or other applications.

B. Acne Treatment Device Using Spatial Modulation Output FIGS. 51A and 51B show a second embodiment of a treatment device for acne (or other possible conditions). The device is similar to the device described above, but the light absorber pattern is created by the output plate of the device rather than a separate patch. In this embodiment, no patch is required and the topical composition is applied directly to the skin 860.

  Looking at FIG. 51A, the applicator 840 of this embodiment can comprise many of the same components as the embodiment of FIGS. For example, the applicator 840 can include a rechargeable battery 846, a charging contact plate 852, a power source 854, an EMR source 862, a reflector 864, a filter 866, and a spring 856 contact plate 858. The charging contact plate 852 provides engagement with the applicator 840 and the charger 850 so that the applicator 840 can be charged. Each of these components may be the same or similar to those described above.

  In the embodiment of FIG. 51A, contact plate 858 includes light absorber 886 in a pattern. In this embodiment, the pattern of optical absorber 886 is robust enough to withstand repeated processing. The light absorber can be made from a corresponding absorbing material, for example carbon powder. The pattern of the light absorber 886 can be integrated with the contact plate 858 so that when the light absorber 886 is heated, this heat can warm the skin 860.

  In operation, the user can apply a topical compound 884 or a pharmaceutical product to the skin 860 over acne injury 861. The user can contact the skin with the contact plate 858 of the applicator 840 and then use the applicator 840 to deliver a pulse of light 880 to the light absorber 886. The light absorber 886 is heated to create a channel pattern with enhanced permeability in the stratum corneum. Alternatively, the local compound 884 can be applied after creating a channel pattern with enhanced permeability in the stratum corneum.

  In the embodiment using a flash lamp, the technical specifications of the treatment device of FIGS. 49 to 51 are summarized in Table E1 below. These embodiments can be used for many applications, including skin diseases and cosmetic treatments.

Deep Tissue Processing The present invention provides a means for creating a non-uniform temperature profile (MTP) deep in the dermis and subcutaneous tissue (generally greater than 500 μm). In some embodiments, such a profile forms a pattern (grid) of isolated points (LID). Active or passive cooling is applied to the epithelial surface to prevent epithelial damage. As described above, the technique of the present invention combines the excellent characteristics of the non-abrasive division technique. The creation of MTP brings improvements to skin structure and texture through the following mechanisms (not just those listed here):
1. Skin lifting and tension as a result of contraction of collagen fibers exposed to high temperatures (immediate effect).
2. Lift and tension the skin as a result of local coagulation within the dermis or subcutaneous tissue (immediate to short term effects).
3. Improvement of skin texture (immediate to short-term effect) as a result of coagulation of the area within the dermis and subcutaneous tissue.
4. Promotion of collagen production by tissue healing response to heat stress or heat shock (mid to long term effect).

The technique can be used to treat a variety of other local and systemic pathologies:
1. Acne Treatment Sebaceous glands can be selectively destroyed by selecting the wavelength of light radiation, promoting selective absorption of EMR energy by sebum, and / or preferential targeting of sebaceous glands.
2. Treatment of hypertrophic scars Deformation from abnormal connective tissue to normal tissue can be initiated by inducing contraction and adhesion in the scar tissue.
3. Reduction of body odor By selectively targeting the eccrine glands, production of eccrine sweat can be reduced and its composition can be changed.
4. Smoothing surfaces other than the skin. The technique can be used to enlarge an organ (eg, lips).
5. Cellulite. By changing the mechanical stress distribution at the dermis / subcutaneous tissue boundary, the appearance of cellulite can be improved.

It is thought that the angular distribution of the skin is neither Gaussian nor Lambertian. In fact, it is nearly non-uniform. In further study, we used a 90-degree Gaussian angular distribution across the width (1 / e ² level). The transverse strength distribution was estimated to be uniform.

  A type II skin was stimulated using a light source having a black body spectrum at 3000 K, such as a halogen lamp. Heat generation at a specific rate was normalized to the incident light flux, and the value obtained was expressed in 1 / cm. The passbands are 0.9-1.3; 0.9-1.5; 0.9-1.8 μm. The depth in the tissue is 2 and 3 mm. As a result, we have six combinations.

Damage profile To evaluate the damage profile, the following model was used: Monochromatic light was applied to a type II skin through a 5 mm thick sapphire plate. Initial plate temperature is 0 ° C. The plate surface opposite the skin is maintained at a fixed temperature of 0 ° C. Light is monochromatic light. There are three stages: pre-cooling, light treatment and post-cooling. A sapphire plate with a transparent mirror and a dielectric mirror coating is always in contact with the skin. The light divergence distribution is evaluated using the MC routine, and then the divergence data is used to evaluate temperature and damage kinetics. The beam is 7mm in diameter and the full angle of divergence is 90 degrees on the skin.

  With a reasonable choice of incident fluence, the damage zone is 1-6 mm in diameter, which is smaller than the beam diameter. With a processing time of 10 seconds, the depth of the damage zone is 2 to 2.8 mm (1064 nm), about 2 mm (1270 nm), about 1.5 mm (1700 nm), 1.1 to 1.2 nm (1560 nm) depending on the processing time. (The longer the processing time, the deeper the damage zone). The properties of the damaged zone were almost independent of pre-cooling and post-cooling. When a parallel beam was used instead of diverging light, the light flux decreased slightly, but the location and shape of the damaged zone remained almost unchanged. The damage zone was almost rested at 1064 and 1270 nm, and was slightly crushed in the vertical direction at 1700 and 1560 nm. It appears that the distance between the spots must be at least 1.5 mm greater than the spot diameter.

Experimental Results A device with a suitable filter, based on a tungsten halogen lamp, outputs radiation from 800 nm to 3.0 mm, adjustable in fluence and pulse width from 1 to 15 J / cm ² . This device also has a sapphire window interface that contacts the sample tissue through which radiation is applied. The beam diameter is fixed at 8mm. A full thickness, domestic pig skin was prepared and placed on a heated pad, with the underlayer (fat and subcutaneous tissue) at about 35 ° C and the surface temperature at about 30 ° C. The sapphire window was cooled to about 10 ° C. using a water cooling line and a cooling device. In one experiment, the device was placed in contact with the pig's skin for a pre-cooling period prior to turning on the treatment lamp.

  FIG. 51 (ac) demonstrates that the skin is stretched without damaging the epithelium. Next, each of the four square faces on the upper left was irradiated once (FIG. 51b), and then the treatment was applied to the four squares on the lower left (FIG. 51c).

  A clear distortion of the skin surface is observed (as seen by the distortion of the grid lines), suggesting that the treatment has contracted. The LDH staining in FIG. 52 reveals the extent of thermal damage applied to the tissue. The injury zone was 4-5 mm long and 1 mm thick just below the epithelial layer. Treatment did not damage the epithelium.

Equivalents While the invention has been particularly shown and described with reference to preferred embodiments thereof, those skilled in the art will recognize that the invention has forms and details without departing from the spirit and scope of the invention as defined by the appended claims. You will understand that various changes can be made. Those skilled in the art will recognize or be able to ascertain that many are equivalent to the particular embodiments of the invention specifically described herein without undue experimentation. Such equivalents are intended to be encompassed by the appended claims.

The figure which shows the cross-sectional example of human skin. Schematic showing the skin phase. FIG. 2 is a semi-schematic perspective view and side view of a patient's skin and device placed thereon to perform one embodiment. FIG. 6 is a top view showing various matrix arrays of cylindrical lenses, some of which are suitable for providing a linear focus at multiple target locations. 1 is a schematic side view of several components that can be used in some aspects of the invention. FIG. 1 is a side view of several handpieces that can be used in some aspects of the invention. FIG. FIG. 6 is a perspective view of another aspect of the invention. FIG. 6 is a perspective view of yet another aspect of the invention. The side view of another aspect of invention. The enlarged side view of the front-end | tip part of the aspect of FIG. 9A. The side view of another aspect of invention. The enlarged side view of the front-end | tip of the aspect of FIG. 10A. The side view of another aspect of invention. The side view of the aspect of the invention using a diode laser bar. FIG. 12B is a perspective view of a diode laser bar that can be used in the embodiment of FIG. 12A. FIG. 5 is a side view of yet another aspect of the invention using a plurality of diode laser bars. FIG. 5 is a side view of yet another aspect of the invention using a plurality of diode laser bars. FIG. 5 is a side view of yet another aspect of the invention that uses multiple optical fibers to couple optical energy. FIG. 3 is a side view of another embodiment of the invention. FIG. 13B is a perspective view of a light source and optical fiber that can be used with the embodiment of FIG. 13A. The side view of the aspect of the invention using a fiber bundle. FIG. 13B is a bottom view of the embodiment of FIG. 13C. FIG. 14 is a side view of one tip of the embodiment of FIGS. FIG. 4 is a side view of another embodiment of the invention using fiber bundles. FIG. 6 is a side view of another aspect of the invention using a phase mask. FIG. 4 is a side view of another embodiment of the invention using multiple laser rods. FIG. 4 is a bottom view of another embodiment of the invention using one or more capacitive imaging arrays. FIG. 4 is a side view of another aspect of the invention in which a motor can be used to move a diode laser bar in the handpiece. FIG. 3 is a top view of one embodiment of a diode laser bar. FIG. 18 is a side sectional view of the diode laser bar of FIG. FIG. 4 is a top view of three types of optical systems comprising an array of optical elements suitable for use in parallel radiation delivery to a plurality of target portions. FIG. 3 is a side view of various lens arrays suitable for delivering parallel radiation to multiple target portions. 1 is a side view of a Fresnel lens array suitable for delivering parallel radiation to multiple target portions. FIG. 1 is a side view of a holographic lens array suitable for use in parallel radiation delivery to multiple target portions. FIG. FIG. 3 is a side view of a tilt lens suitable for use in parallel radiation delivery to multiple target portions. FIG. 6 is a top view of various matrix arrays of cylindrical lenses, some of which are suitable for providing a linear focus on multiple target portions. FIG. 6 is a cross-sectional or side view of a single layer matrix cylindrical lens system suitable for delivering radiation parallel to a plurality of target portions. FIG. 2 is a perspective view and a cross-sectional side view, respectively, of a two-layer cylindrical lens array suitable for delivering parallel radiation to a plurality of target portions. FIG. 4 is a side view of various optical objective arrays suitable for use in concentrating radiation on one or more target portions. FIG. 14 is a side view of various deflection plates suitable for use with the array of FIGS. 10-13 and for moving successive target portions. FIG. 2 is a side view of two variable focusing optical systems suitable for use in practicing the teachings of the present invention. FIG. 7 is a perspective view of another aspect of the invention for creating a process isolation point. The side view of another aspect of invention. FIGS. 3A and 3B are a side view and a top view, respectively, of an embodiment of the invention having skin lifting means such as a vacuum. The side view of another aspect of invention. FIG. 43B is a side view of the distal end portion of the embodiment of FIG. 43A. FIG. 43B is an enlarged bottom view of the tip portion of the aspect of FIG. 43A. FIG. 6 is a perspective view of another aspect of the present invention for creating a processing isolation point. 2 is a perspective view of two scenes of another aspect of the present invention for creating a processing isolated point. FIG. FIG. 6 is a perspective view of another aspect of the present invention for creating a processing isolation point. The side view of the aspect of invention using the film with an active isolated point. FIG. 6 is a perspective view of another aspect of the present invention for creating a processing isolation point. FIG. 6 is a side view of various aspects of the present invention for creating a processing isolation point. Explanatory drawing of an Example. 4 is a diagram of a four-layer skin model used for the computer model described in Example 1. FIG. FIG. 6 shows the threshold fluence of skin damage as a function of wavelength at depths of 0.25 mm (1), 0.5 mm (2) and 0.75 mm (3) in the adiabatic mode. The figure which shows the optical penetration depth vs. wavelength in the type II skin of the circular beam with a diameter of 0.1 mm applied to the skin through sapphire. Normalized irradiance on the beam axis as a function of skin depth for wavelengths of 800 (1), 1060 (2), 1200 (3), 1440 (4), 1500 (5) and 1700 (6) nm Illustration. Normalized radiation on the beam axis, expressed as a function of depth, of 1064 nm light focused at skin depths of 0.5 (1), 0.6 (2), 0.7 (3) and 1 (4) mm Illuminance diagram. FIG. 3 shows tissue irradiance vs. depth for parallel beams of 10 mm (1) and 0.1 mm (2) diameters through a sapphire at a wavelength of 1060 nm applied to a type II skin surface.

Claims (285)

An apparatus for applying a treatment to a target area of a patient's skin,
a) a housing having a portion defining a target treatment area on the patient's skin when placed near the patient's skin; and
b) comprising an LED bar mounted in a housing for applying optical energy to the target area, wherein the LED bar provides an optical energy emitter for creating a treatment isolated point on the patient's skin; A plurality of devices. An apparatus for applying a treatment to a target area of a patient's skin,
a) a housing having a portion defining a target treatment area on the patient's skin when placed near the patient's skin; and
b) comprising a diode laser bar mounted in a housing for applying optical energy to the target area, wherein the diode laser bar provides optical energy for creating a treatment isolated point on the patient's skin. A device comprising a plurality of emitters. The apparatus of claim 2, wherein the emitters are spaced such that optical energy acts on a plurality of subregions. The apparatus of claim 3, wherein the emitters are spaced about 50-900 μm apart. The apparatus of claim 2, wherein the emitter emits light in the wavelength range of about 290-10,000 nm. 6. The apparatus of claim 5, wherein the emitter emits light in the wavelength range of about 900 to 10,000 nm. The apparatus of claim 5, wherein the emitter has a width of about 50-150 μm. 6. The apparatus of claim 5, wherein the diode laser bar has a length of about 1 cm. 9. The apparatus of claim 8, wherein the diode laser bar is about 1 mm wide. The apparatus of claim 2, wherein the diode laser bar comprises 10 to 15 emitters. The apparatus of claim 2, wherein the apparatus comprises more than one diode laser bar. 12. The apparatus of claim 11, wherein the apparatus comprises 5 or more diode laser bars. 12. The apparatus of claim 11, wherein the diode laser bar is made in the form of a bundle that creates a matrix of treated isolated points on the patient's skin in use. The apparatus of claim 2, further comprising one or both of a cooling element and / or a heating element attached to the housing. 15. The apparatus of claim 14, wherein the cooling element is placed between the diode laser bar and a patient's skin in use. 15. The apparatus of claim 14, wherein the cooling element is capable of passing at least a portion of the optical energy from the diode laser bar. 17. The apparatus of claim 16, wherein the cooling element provides cooling to all areas in contact with the patient's skin. 17. The apparatus of claim 16, wherein the cooling element creates a cooling isolation point between process isolation points. 3. The apparatus of claim 2, wherein the portion of the housing that defines a target treatment area comprises a cooling element, the cooling element being disposed between the diode laser bar and the patient's skin in use. 3. The apparatus of claim 2, further comprising a speed sensor that measures the speed of movement of the housing across the patient's skin. 21. The apparatus of claim 20, further comprising a circuit that changes the output power of the diode laser bar in response to the speed of movement of the housing across the patient's skin. 22. The apparatus of claim 21, further comprising a circuit that controls an interval between pulses of the diode laser bar such that the interval is inversely proportional to the speed of movement of the housing across the patient's skin. 21. The apparatus of claim 20, wherein the speed sensor is a capacitive imaging array. 24. The apparatus of claim 23, wherein the capacitive imaging array creates an image of a processing region in use. 3. The apparatus of claim 2, further comprising a motor that moves the diode laser bar relative to the housing. 26. The apparatus of claim 25, further comprising circuitry for controlling the motor to move the diode laser bar in a direction opposite to the direction of movement of the housing across the patient's skin. 3. The apparatus of claim 2, further comprising one of an imaging, reflective or diffractive optical element disposed between the diode laser bar in the housing and a portion of the housing that defines a target processing area. 3. The device of claim 2, wherein the housing has a head portion that contacts the skin during use. 30. The apparatus of claim 28, further comprising a contact sensor that senses that the head is in contact with the patient's skin. The apparatus of claim 2, further comprising a mechanism coupled to the plurality of emitters for creating a treatment isolation point on the patient's skin. 32. The apparatus of claim 30, wherein the mechanism is a lens array. 32. The apparatus of claim 30, wherein the mechanism is a bundle of optical fibers, each of the fibers connected to at least one emitter. The device of claim 2, wherein the device is a handheld device. The apparatus of claim 2, further comprising an optical element associated with each emitter, said optical element assisting in the creation of a processing isolation point. 3. The apparatus of claim 2, further comprising a sensor that detects one or more of contact, speed, and imaging. 3. The device of claim 2, wherein in use, the output from the emitter is in the range of about 50 to 1000 microns of human skin. The apparatus of claim 2, wherein the distance between the output from the emitter and the output from the housing is in the range of about 50 to 1000 microns. The apparatus of claim 2, wherein the distance between the output from the emitter and the output from the housing is in the range of about 50 to 1000 microns. Handheld dermatology device:
A housing that can be manually operated to place the housing head near the human skin, wherein the head defines a target treatment area of the human skin;
A diode laser bar supported by the housing having a plurality of optical energy emitters; and one of a cooling or heating surface associated with the housing, the cooling or heating surface being in use by the patient A device that touches the skin of the laser and creates output isolation points in the target processing area where the output radiation from the diode laser bar passes through the cooling surface. 40. The handheld dermatological device of claim 39, wherein the cooling or heating surface is a sapphire plate. 40. The handheld dermatological device of claim 39, further comprising a diffractive optical element for converging output radiation disposed in an optical path between the diode laser bar and the cooling or heating surface. 40. The emitter of claim 39, wherein the emitters are spaced such that optical energy acts on a plurality of subregions in human skin, while not affecting a substantial portion of the target region between subregions. Dermatology equipment. An apparatus for applying treatment to a target area of a patient's skin comprising a light emitting assembly for applying optical energy to the target area, the light emitting assembly comprising a plurality of emitters of optical energy A device comprising a bar, wherein the optical energy acts on the subregions without affecting a substantial portion of the target region between the subregions. An apparatus further comprising a heating element attached to the light emitting assembly, wherein the heating element is disposed between the light emitting assembly and a target area of a patient's skin and uses the apparatus to heat the target area. 44. The apparatus of claim 43, wherein the device is in contact with the target area while the heating element is capable of passing at least a portion of the optical energy from the light emitting assembly therethrough. And further comprising a cooling element attached to the light emitting assembly, the cooling element being disposed between the light emitting assembly and a target area of the patient's skin while cooling the target area with a device. 44. The apparatus of claim 43, in contact with a target area, wherein the cooling element is capable of passing at least a portion of the optical energy from the light emitting assembly therein. 46. The apparatus of claim 45, wherein the cooling element is made of sapphire or diamond. 46. The apparatus of claim 45, wherein the cooling element is made of an optically transmissive material. 44. The apparatus of claim 43, wherein the light emitting assembly comprises a plurality of diode laser bars in a bundled form. 49. The apparatus of claim 48, wherein the plurality of diode laser bars emit different wavelengths of radiation. 44. The apparatus of claim 43, wherein the optical energy source is in the handpiece. 44. The apparatus of claim 43, wherein the optical energy source is in a separate base unit. 44. The apparatus of claim 43, wherein the optical energy source emits light having a wavelength in the range of about 290 to 10,000 nm. 44. The apparatus of claim 43, wherein the output from the emitter is in use in the range of about 50-1000 microns of the patient's skin. The light emitting assembly includes a housing for the diode laser bar, the housing having an output plate for placement near the patient's skin during use, the output from the emitter and the output area of the output plate 44. The apparatus of claim 43, wherein the distance between is in the range of about 50 to 1000 microns. 44. The apparatus of claim 43, further comprising an element for creating a processing isolated point selected from the group consisting of a diffractive optical element and a mask. An apparatus for treating a target area of a patient's skin by applying optical energy to the target area, comprising:
a) an optical energy source;
b) an applicator capable of moving to a target area proximate position on the patient's skin to apply optical energy to the target area; and
c) comprising one or more optical fibers for transmitting optical energy from the optical energy source to the applicator;
An apparatus wherein the applicator comprises a mechanism for delivering optical energy onto a target area, and the apparatus creates an isolated point of processing. 57. The apparatus of claim 56, wherein the optical energy delivery mechanism is a total internal reflection element. 57. The apparatus of claim 56, wherein the optical energy source is selected from the group consisting of LEDs, lasers, diode laser bars, radiant lamps, halogen lamps, incandescent lamps, arc lamps, and fluorescent lamps. 57. The apparatus of claim 56, wherein the applicator is a handpiece. 57. The apparatus of claim 56, wherein the optical energy source is disposed within a handpiece. 57. The apparatus of claim 56, wherein the optical energy source is disposed in a separate base unit. 57. The apparatus of claim 56, wherein the optical energy source creates a damaged isolated point. 57. The apparatus of claim 56, wherein each optical fiber provides an independent beam of light. 57. The apparatus of claim 56, further comprising a re-imaging optical series. A housing that can be manually operated to place the head of the housing near the human skin, the head defining a target treatment area of the human skin; and coupling radiation from the radiation source to the human skin via the handpiece A hand-held dermatological device comprising a plurality of optical fibers in the housing, wherein the optical fibers are spaced apart to create a processing isolation point. 68. The apparatus of claim 65, wherein the radiation source is disposed within a handpiece. 66. The apparatus of claim 65, wherein the radiation source is located in a separate base unit. An apparatus for applying treatment to a target area of a patient's skin:
a) a light emitting assembly for applying optical energy to a target area of the patient's skin, wherein the light emitting assembly is movable across the target area of the patient's skin, and from the light emitting assembly A light emitting assembly including an optical energy source for outputting optical energy, wherein the radiation source is movably attached to the head;
b) a sensor for measuring the speed of movement of the head across the target area of the patient's skin; and
c) controlling the movement of the source relative to the head based on the speed of movement of the head across the target area of the patient's skin to form a treatment isolated point in the target area of the patient's skin; A device comprising a circuit in communication with a sensor. 69. The apparatus of claim 68, wherein the circuit controls movement of the source such that the source remains generally stationary relative to the target as the head moves relative to the target area. The circuit moves the radiation source, and the radiation source moves from a first position in the head portion to a second position in the head portion in a direction generally opposite to the movement direction of the head portion. 69. The apparatus according to claim 68, wherein the apparatus moves at approximately the same speed and controls to return to the first position when the source reaches the second position. 69. The apparatus of claim 68, wherein the radiation source is attached to a rectilinear motion body within the head portion. 69. The apparatus of claim 68, wherein the radiation source is attached to a rotatable cylindrical shaft. 69. The apparatus of claim 68, wherein the optical energy source is selected from the group consisting of LEDs, lasers, diode laser bars, radiant lamps, halogen lamps, incandescent lamps, arc lamps, and fluorescent lamps. 69. The apparatus of claim 68, wherein the sensor comprises one or more capacitive imaging arrays. 75. The apparatus of claim 74, wherein the capacitive imaging array images a processing region for real-time or later confirmation. 75. The apparatus of claim 74, wherein the capacitive imaging array is disposed on front and back sides of the head portion, and the head portion can be moved back and forth. 69. The apparatus of claim 68, wherein the sensor is a wheel with a rotational frequency meter. 78. The apparatus of claim 77, wherein the sensor is an optical encoder. 69. The apparatus of claim 68, wherein the entire light emitting assembly is in a handpiece or has a source in a separate base unit. 69. The apparatus of claim 68, further comprising an element that creates a process isolation point, wherein the element is selected from the group consisting of a diffractive optical element, a filter, and a mask. 69. The apparatus of claim 68, further comprising a cooling element in contact with the skin. 84. The apparatus of claim 81, wherein the cooling element is made of sapphire or diamond. An apparatus for applying treatment to a target area of a patient's skin:
a) a light emitting assembly with a non-interfering light source for applying optical energy to the target area; and
b) comprising a plurality of light directing elements at the output end of the light emitting assembly, said light directing elements being substantially free of light through the output end when the output end is not in contact with the patient's skin And wherein the light directing element creates a treatment isolated point on the patient's skin. 84. The apparatus of claim 83, wherein the light source is selected from the group of a linear flash lamp, an arc lamp, an incandescent lamp, and a halogen lamp. 84. The apparatus of claim 83, wherein the light directing element is selected from the group consisting of an array of triangular pyramids, cones, hemispheres, grooves and prisms. A housing that can be manually operated to place the housing head near the human skin, wherein the head defines a target treatment area of the human skin;
An optical path between an energy source and the head;
A dermatological device comprising a plurality of light directing elements for directing light from an energy source, wherein the light directing element is substantially free of light when the output end is not in contact with the patient's skin. A dermatological device, shaped so as not to pass through the output end, wherein the light directing element creates a treatment isolation point on the patient's skin. An apparatus for applying treatment to a target area of a patient's skin:
a) a light emitting assembly with a non-interfering light source for applying optical energy to the target area; and
b) an apparatus comprising an optically diffusing surface having an optically transmissive spot for spatially modulating the output light at the output end of the light emitting assembly. 88. The apparatus of claim 87, wherein the light source is selected from the group of a linear flash lamp, an arc lamp, an incandescent lamp, and a halogen lamp. 88. The apparatus of claim 87, further comprising one or more of said light directing elements selected from the group consisting of reflectors, filters and light ducts. 88. The apparatus of claim 87, wherein the one or more light directing elements are selected from the group consisting of an array of triangular pyramids, cones, hemispheres, grooves and prisms. 90. The apparatus of claim 87, wherein the optically transmissive spot can have a variety of shapes. 92. The apparatus of claim 91, wherein the optically transmissive spot is one or more circles, slits, rectangles, ellipses or irregular shapes. A light emitting assembly that applies treatment to a target area of a patient's skin comprising:
a) a non-interfering light source; and
b) a light emitting assembly comprising a light guide for delivering optical energy from the light source to a target area, the light guide comprising a bundle of optical fibers, the bundle of optical fibers creating a treatment isolation point on the patient's skin; . 94. The light emitting assembly of claim 93, wherein the light guide is made of a bundle of fibers doped with rare earth metal ions. 94. The light emitting assembly of claim 93, wherein the fiber surrounds the light source. 94. The light emitting assembly of claim 93, wherein a microlens is attached to the output end of the light guide. 94. The light emitting assembly of claim 93, wherein the light source is selected from the group of a linear flash lamp, an arc lamp, an incandescent lamp, and a halogen lamp. 94. The light emitting assembly of claim 93, further comprising a filter between the light source and the light guide. 94. The light emitting assembly of claim 93, further comprising a reflector surrounding a portion of the light source. A light emitting assembly for use in treating a target area of a patient's skin comprising:
A non-interfering light source; and a plurality of light guides, each light guide delivering optical energy from a different light source to a target area, wherein the plurality of light guides provide spatial light modulation. 101. The light emitting assembly of claim 100, wherein the output ends of the plurality of light guides create a treatment isolation point on the patient's skin. 101. The apparatus of claim 100, wherein the light source is selected from the group of a linear flash lamp, an arc lamp, an incandescent lamp, and a halogen lamp. 101. The apparatus of claim 100, further comprising a filter between the light source and the light guide. 101. The apparatus of claim 100, further comprising a reflector surrounding a portion of the light source. An apparatus for applying treatment to a target area of a patient's skin:
a) a light emitting assembly for applying optical energy from an optical energy source to the target area; and
b) comprising a mask attached to the light emitting assembly, wherein the mask is located between the optical energy source and the target area during use of the apparatus, the mask comprising one or more dielectric layers, A device comprising a plurality of openings through which optical energy from the optical energy source reaching the target region passes. 106. The apparatus of claim 105, wherein the dielectric layer has a high reflectivity over the entire spectral band emitted by the optical energy source. 106. The apparatus of claim 105, wherein the optical energy source is selected from the group consisting of LEDs, lasers, diode laser bars, radiant lamps, halogen lamps, incandescent lamps, arc lamps, and fluorescent lamps. 106. The apparatus of claim 105, wherein the opening has various shapes. 109. The apparatus of claim 108, wherein the shape of the opening is one or more lines, circles, slits, rectangles, ovals or irregular shapes. 106. The apparatus of claim 105, wherein the openings are the same shape. 106. The apparatus of claim 105, wherein an edge of the opening is anti-reflective coated. 106. The apparatus of claim 105, further comprising a Fresnel lens or refractive lens for shaping the angle beam. 106. The apparatus of claim 105, wherein the apparatus comprises one or more cooling or heating elements for cooling or heating the mask during use. 114. The device of claim 113, wherein the cooling element cools the patient's skin during use. 106. The apparatus of claim 105, wherein the cooling element cools the light emitting assembly. 106. The device of claim 105, wherein the cooling device cools the components of the device during use. 106. The apparatus of claim 105, further comprising a waveguide for homogenizing a light beam from the optical energy source. 106. The apparatus of claim 105, further comprising a temperature monitoring mechanism for monitoring the temperature of the target area. 119. The apparatus of claim 118, wherein the optical energy is in the infrared band. 120. The apparatus of claim 119, wherein the optical energy is in the near infrared band. 120. The apparatus of claim 119, wherein the optical energy operates at a pulse width of 100 fetoseconds to 1 second. A housing that can be manually operated to place the housing head near the human skin, wherein the head defines a target treatment area of the human skin;
An optical path between an energy source and the head;
A dermatological device comprising a mirror with a hole,
A dermatological device wherein the mirror is in the optical path and the hole allows optical energy to pass from an energy source to a target treatment area. A housing that can be manually operated to place the head of the housing near the human skin, the head defining a target treatment area of the human skin; and a light path between a laser energy source and the head A dermatological apparatus, wherein the laser energy source includes a reflector, and the output from the reflector includes a region where the reflectance is lower than that of other regions of the reflector, and the region where the reflectance is low is used. A dermatological device that creates isolated spots inside. 124. The dermatological device of claim 123, wherein the low reflectivity region serves as a hole for passing optical energy from the laser energy source to the target processing region. An apparatus for applying treatment to a target area of a patient's skin under a skin wrinkle comprising two light emitting assemblies for applying optical energy to the target area, the light emitting assembly comprising: A device that is directed to emit light beams that intersect at a target area of the patient's skin from approximately opposite sides of the eyelid. 126. The apparatus of claim 125, wherein the light emitting assembly can comprise an LED, laser, diode laser bar, radiant lamp, halogen lamp, incandescent lamp, arc lamp or fluorescent lamp. 126. The apparatus of claim 125, further comprising a mechanism for creating a processing isolated point using optical energy. 128. The apparatus according to claim 127, wherein the mechanism for creating the processing isolated point is selected from one or more diffractive optical elements, masks or filters. A method for applying treatment to a target area of a patient's skin under a skin wrinkle:
Lifting the patient's skin to create wrinkles in the skin; and applying a light beam from approximately opposite sides of the skin's wrinkle to cause the light beam to intersect at the target area of the patient's skin. 129. The method of claim 129, further comprising creating a processing isolated point using the light beam. An apparatus for applying treatment to a target area of a patient's skin:
A skin lifting device that lifts and stretches a target area of the underlying skin; and a light emitting assembly for applying optical energy to the target area, wherein the light emitting assembly emits light toward the patient's skin . 132. The apparatus of claim 131, wherein the skin lifting device is a vacuum source. A composition for use in treating a target area of a patient's skin comprising a material that can be selectively applied to a portion of the target area of the patient's skin, the material comprising an absorbable exogenous chromophore, A composition in which the action of optical energy on the material selectively heats a portion of the target area. 134. The composition of claim 133, wherein the composition comprises a high concentration of chromophore. 139. The composition of claim 134, wherein the composition creates a processing isolation point in the entire processing region because of its high concentration. 134. The composition of claim 133, wherein the chromophore is dispersed in the composition and only the portion of the composition having the chromophore is heated by the action of optical energy. 138. The composition of claim 136, wherein the optical energy is applied to the entire composition such that only a portion of the composition having the chromophore can be heated. 134. The composition of claim 133, wherein the optical energy is produced with a radiation source selected from the group consisting of LEDs, lasers, diode laser bars, radiant lamps, halogen lamps, incandescent lamps, arc lamps or fluorescent lamps. 134. The composition of claim 133, wherein the chromophore is carbon, metal, organic dye, non-organic dye or fullerene. 134. The composition of claim 133, wherein the composition can be printed on a patient's skin using a print head. 145. The composition of claim 143, wherein the printhead is in a handheld device that includes an optical energy source. 134. The composition of claim 133, wherein the composition is arranged in one or more dots, lines or irregular shapes. 134. The composition of claim 133, wherein the composition is a fiber or yarn mesh. Substances for use in treating a target area of a patient's skin, including:
a) a film applicable to a target area of the patient's skin; and
b) comprising a composition containing an absorbing exogenous chromophore,
A substance in which the composition is selectively fixed to a portion of the film and the action of optical energy on the composition selectively heats a portion of the target area proximate to the composition. 145. The material of claim 144, wherein the optical energy is produced by a source selected from the group consisting of LEDs, lasers, diode laser bars, radiation lamps, halogen lamps, incandescent lamps, arc lamps or fluorescent lamps. 145. A substance according to claim 144, wherein the chromophore is carbon, metal, organic dye, non-organic dye or fullerene. 145. A material according to claim 144, wherein the film is an optically transparent polymer. 145. The substance of claim 144, wherein exposure to light causes an exothermic reaction between at least two constituents of the composition. A kit for use in treating a target area of a patient's skin comprising:
A material that can be selectively applied to a portion of the target area of the patient's skin and that includes an absorbing extrinsic chromophore; and a light emitting assembly for applying optical energy to the target area of the patient's skin, to the material A kit in which the action of optical energy from said light emitting assembly heats a portion of the target area of the patient's skin. 150. The kit of claim 149, wherein the optical energy has one or more wavelength bands that match the absorption spectrum of the absorbing foreign chromophore. 150. The kit of claim 149, wherein the material is a patch for application to a patient's skin. 150. The kit of claim 149, wherein the material is a lotion for application to the patient's skin. A dermatological device that can be manually operated to place a head portion of a housing near a human skin, the head portion defining a target treatment area of the human skin; and a substrate having a plurality of absorbent elements An apparatus in which incident radiation from an energy source heats an absorbing element, creating an isolated point in the stratum corneum of human skin. 154. The dermatological device of claim 153, wherein the substrate is a mask that blocks incident radiation to areas of the mask that do not have an absorbing element. 154. A dermatological device according to claim 153, wherein the mask is shaped on a contact plate. 165. A dermatological device according to claim 155, wherein the contact plate is a cooling plate. 165. A dermatological device according to claim 155, wherein the contact plate forms the head portion of the housing. 154. A dermatological device according to claim 153, wherein the absorbent element is carbon. 154. The dermatological device of claim 153, wherein the energy source is in the housing. 154. A dermatological device according to claim 153, wherein the energy source is a base unit independent of the housing. A substrate having a plurality of absorbing elements, wherein the absorbing elements are heated by incident radiation from an energy source to create an absorption isolated point in the stratum corneum of the patient's skin; and a composition contained on at least one side of the substrate A dermatological delivery device comprising an article, wherein at least a substantial portion of the composition remains on the patient's skin after removal of the substrate. 164. The dermatological delivery device of claim 161, wherein a portion of the composition penetrates the stratum corneum of the patient's skin by the creation of a treatment isolation point. A light emitting assembly for use in treating a target area of a patient's skin comprising:
a) Solid state laser
b) a fiber bundle for receiving optical energy from the laser and spatially modulating the optical energy from the laser to create a treatment isolated point in the patient's skin; and
c) An assembly comprising a focusing optical system at the output end of the fiber bundle for projecting optical energy from each fiber of the fiber bundle onto a target area. 164. The light emitting assembly of claim 163, wherein the laser active rod is made of garnet doped with rare earth ions. 164. The light emitting assembly of claim 163, wherein the focusing optics comprises a microlens array. A light emitting assembly for use in treating a target area of a patient's skin comprising:
a) Solid state laser
b) a fiber bundle for receiving optical energy from the laser; and
c) a focusing optical system at the output end of the fiber bundle for projecting optical energy from each fiber of the fiber bundle onto a target area, and the focusing optical system spatially modulates the optical energy of the laser to form a patient's skin Light emitting assembly that creates isolated points in the process. A light emitting assembly for use in treating a target area of a patient's skin comprising:
a) solid state laser;
b) a phase mask comprising a plurality of openings for transmitting radiation from the laser; and
c) A light emitting assembly comprising a converging optical system at the output end of the phase mask that provides spatial light modulation to the target area. 168. The light emitting assembly of claim 167, wherein the phase mask creates a treatment isolated point on the patient's skin. 170. The light emitting assembly of claim 167, wherein the laser active rod is made of garnet doped with rare earth ions. 169. The light emitting assembly of claim 167, further comprising a reflector near the laser. 169. The light emitting assembly of claim 167, further comprising an output coupler at the output end of the laser. 168. The light emitting assembly of claim 167, wherein the focusing optics comprises a microlens array. A light emitting assembly for use in treating a target area of a patient's skin comprising:
a) a bundle of fiber lasers; and
b) Optical radiation at the output end of the bundle comprising focusing optics for focusing the radiation of each laser onto a target area, the bundle of fiber lasers and the focusing optics creating a treatment isolated point on the patient's skin Assembly. 174. The light emitting assembly of claim 173, wherein the laser active rod is made of garnet doped with rare earth ions. 174. The light emitting assembly of claim 173, further comprising a reflector in the light source. 174. The light emitting assembly of claim 173, further comprising an output coupler at an output end of the laser bundle. 174. The light emitting assembly of claim 173, wherein the focusing optics comprises a microlens array. An apparatus for use in applying treatment to a target area of a patient's skin comprising:
a) a light emitting assembly for applying optical energy to the target area; and
b) comprising an element attached to the light emitting assembly, wherein the element is placed between the light emitting assembly and a labeled area of the patient's skin when the device is in use, and the element receives light from the light emitting assembly; An apparatus comprising in the reflective material a reflective material that reflects energy to the light emitting assembly and an aperture through which optical energy from the light emitting assembly can pass. 181. The apparatus of claim 178, wherein the light emitting assembly comprises a radiation source selected from the group consisting of LEDs, lasers, diode laser bars, radiant lamps, halogen lamps, incandescent lamps, arc lamps or fluorescent lamps. 181. The apparatus of claim 178, wherein the light emitting assembly is surrounded by a reflective material. 181. The apparatus of claim 178, wherein the light is pumped into a box that includes one or more reflective surfaces. 181. The apparatus of claim 181, wherein the reflective surface is a perforated mirror. An apparatus for use in applying treatment to a target area of a patient's skin comprising:
a) a light emitting assembly comprising a light source for applying optical energy to the target area; and
b) comprising a plurality of light directing elements attached to the output end of the light emitting assembly for spatially modulating and collecting the output light, the optical energy acting on a plurality of small areas, A device that does not affect a substantial portion of the target area between the areas. 184. The apparatus of claim 183, wherein the light source is a non-interfering light source. 188. The apparatus of claim 183, wherein the light source is selected from the group of linear flash lamps, arc lamps, incandescent lamps and halogen lamps. 184. The apparatus of claim 183, wherein the light directing element is selected from the group consisting of a reflector, a mask, or a light duct. 184. The apparatus of claim 183, wherein the light directing element comprises a microarray lens. 184. The apparatus of claim 183, wherein the one or more light directing elements are selected from the group consisting of an array of pyramids, cones, hemispheres, grooves and prisms. 184. The apparatus of claim 183, wherein the light source is an interference light source. 189. The apparatus of claim 189, wherein the light source is selected from the group comprising a solid state laser, a fiber laser and a dye laser. 189. The apparatus of claim 189, wherein the light source is a laser active rod made from garnet doped with rare earth ions. 189. The apparatus of claim 189, wherein the light source is a fiber laser bundle. 189. The apparatus of claim 189, wherein at least one light directing element is at the output end of each fiber laser to spatially modulate and collect the output light. 189. The apparatus of claim 189, wherein the light emitting assembly comprises a fiber disposed between the light source and the light directing element, the fiber receiving optical energy from the light source. 195. The apparatus of claim 194, wherein a fiber bundle spatially modulates optical energy from the light source. 195. The apparatus of claim 195, wherein the light directing element is a focusing optics at the output end of the fiber for projecting light energy from each fiber of the fiber bundle onto the target area. A housing that can be manually operated to place the housing head near the human skin, wherein the head defines a target treatment area of the human skin;
An optical path between an energy source and the head;
A dermatological device comprising a plurality of light directing elements that focus light from the energy source to create a treatment isolation point in human skin. 197. The dermatological device of claim 197, wherein the plurality of light directing elements is a microlens array. A method for increasing the permeability of a subject's stratum corneum to a compound comprising:
By making EMR radiation act on a part of the stratum corneum of the subject to make a lattice of EMR treatment isolated points on a part of the stratum corneum of the subject,
Heating the lattice of EMR treated isolated points to a temperature sufficient to increase the permeability of a portion of the stratum corneum to the compound. A method for increasing the permeability of a subject's stratum corneum to a compound comprising:
Processing a part of the stratum corneum of the subject with an EMR processing apparatus that creates a grid of EMR processing isolated points on a part of the stratum corneum of the subject,
Heating the EMR-treated isolated point lattice to a temperature sufficient to increase the permeability of a portion of the stratum corneum to the compound. 213. The method of claim 200, wherein the compound is selected from the group consisting of therapeutic agents and cosmetics. 213. The method of claim 200, wherein the compound is a therapeutic agent selected from the group consisting of hormones, steroids, non-steroidal anti-inflammatory agents, antitumor agents, antihistamines and anesthetics. 202. The method described in 1. 213. The method of claim 200, wherein the compound is a cosmetic selected from the group consisting of a pigment, a reflective agent, or a photoprotective agent. Heating the EMR-treated isolated point lattice to a temperature sufficient to at least partially lyse the crystalline lipid extracellular matrix within the EMR-treated isolated point lattice of a portion of the stratum corneum;
200. The method of claim 200, thereby increasing the permeability of a portion of the stratum corneum to the compound. 206. The method of claim 205, wherein the EMR-treated isolated point grid is heated to a temperature of 35-40 <0> C. 206. The method of claim 205, wherein the EMR treated isolated point grid is heated to a temperature of 40-50C. 206. The method of claim 205, wherein the grid of EMR-treated isolated points is heated to a temperature of 50-100 ° C. 206. The method of claim 205, wherein the increase in permeability is reversible after the EMR processor is shut down. 209. The method of claim 209, wherein the increase in permeability is reversed by crystallization of the lipid extracellular matrix within 2 hours after discontinuation of the treatment. 206. The method of claim 205, wherein the increase in permeability is reversed by crystallization of the lipid extracellular matrix within 1 hour after discontinuation of the treatment. 209. The method of claim 209, wherein the increase in permeability is reversed by crystallization of the lipid extracellular matrix within 30 minutes after discontinuation of the treatment. 209. The method of claim 209, wherein the increase in permeability is reversed by crystallization of the lipid extracellular matrix within 15 minutes after discontinuing the treatment. 206. The method of claim 205, wherein the EMR-treated isolated point grid is heated to a temperature insufficient to solidify or denature proteins in the isolated point grid. Heating the grid of EMR treated isolated points to a temperature sufficient to at least partially evaporate water present in the portion of the stratum corneum;
200. The method of claim 200, thereby increasing the permeability of a portion of the stratum corneum to the compound. 215. The method of claim 215, wherein the grid of EMR treated isolated points is heated to a temperature of 100-200C. 215. The method of claim 215, wherein the grid of EMR treated isolated points is heated to a temperature greater than 200 ° C. 213. The method of claim 200, wherein the EMR-processed isolated point grid comprises isolated point multiplicity with each isolated point having a maximum dimension of 1 [mu] m to 30 nm. 218. The method of claim 218, wherein the grid of EMR-treated isolated points comprises isolated point multiplicity with each isolated point having a maximum dimension between 1 [mu] m and 10 nm. 218. The method of claim 218, wherein the grid of EMR-processed isolated points comprises a multiplicity of isolated points, each isolated point having a maximum dimension between 10 [mu] m and 100 [mu] m. 218. The method of claim 218, wherein the grid of EMR treated isolated points comprises a multiplicity of isolated points, each isolated point having a maximum dimension of 100 μm to 1 mm. 218. The method of claim 218, wherein the grid of EMR processed isolated points comprises a multiplicity of isolated points, each isolated point having a maximum dimension of 1 mm to 10 mm. 213. The method of claim 200, wherein the grid of EMR treated isolated points in a portion of the stratum corneum has a fill factor of 0.01-90%. 224. The method of claim 223, wherein a grid of EMR-treated isolated points in a portion of the stratum corneum has a fill factor of 0.01-0.1%. 224. The method of claim 223, wherein the grid of EMR-treated isolated points in a portion of the stratum corneum has a fill factor of 0.1-1%. 224. The method of claim 223, wherein a grid of EMR-treated isolated points in a portion of the stratum corneum has a fill factor of 1-10%. 224. The method of claim 223, wherein the grid of EMR-treated isolated points in a portion of the stratum corneum has a fill factor of 10-30%. 224. The method of claim 223, wherein a grid of EMR treated isolated points in a portion of the stratum corneum has a fill factor of 30-50%. A method for transdermal delivery of a compound to a subject comprising:
Processing a part of the stratum corneum of the subject with an EMR processing apparatus that creates a grid of EMR processing isolated points on a part of the stratum corneum of the subject,
Heating the lattice of the EMR treated isolated points to a temperature sufficient to thereby increase the permeability of a portion of the stratum corneum to the compound. 229. A method according to any one of claims 200 or 229, wherein a portion of the papillary dermis underlying a portion of the stratum corneum is not heated to a temperature above 43 ° C. 229. A method according to any one of claims 200 or 229, wherein a portion of the papillary dermis underlying a portion of the stratum corneum is not heated to a temperature above 40 ° C. A method for increasing the permeability of a subject's stratum corneum to a compound comprising:
Processing a part of the stratum corneum of the subject with an EMR processing apparatus that creates a grid of EMR processing isolated points on a part of the stratum corneum of the subject,
At this time, the device creates a grid of the EMR-treated isolated points by delivering EMR energy to the endogenous chromophore within the isolated points,
Heating the lattice of the EMR treated isolated points to a temperature sufficient to thereby increase the permeability of a portion of the stratum corneum to the compound. 234. The method of claim 232, wherein the endogenous chromophore is selected from the group consisting of water, lipid, or protein. 234. The method of claim 232, wherein the endogenous chromophore is selected from the group consisting of water, melanin, hemoglobin, and collagen. 234. The method of claim 232, wherein the EMR processor creates the EMR-processed isolated point grid by delivering EMR energy to the tissue optical isolated point grid. 235. The method of claim 235, wherein the EMR processor produces a plurality of EMR beams that deliver EMR energy to a lattice of optically isolated points of the tissue. A method for increasing the permeability of a subject's stratum corneum to a compound comprising:
Treating a portion of the subject's stratum corneum with an EMR processor that creates a lattice of thermally isolated points in a portion of the stratum corneum of the subject,
At this time, the device creates a lattice of thermally isolated points by delivering EMR energy to exogenous EMR absorbing particles that are in contact with a portion of the stratum corneum, and the EMR processing device absorbing particles are part of the stratum corneum. A method of transferring the heat to the part to make a lattice of the heat isolated points. The exogenous EMR absorbing particles are present on the surface of the stratum corneum in a spatial arrangement corresponding to the lattice, and the exogenous EMR absorbing particles are heated by a substantially uniform beam of EMR energy from the device 240. The method of claim 237. 238. The method of claim 238, wherein the exogenous EMR absorbing particles are present in a film that is applied to the surface. 238. The method of claim 238, wherein the EMR absorbing particles are present in a lotion applied to the surface. The exogenous EMR absorbing particles are present on the surface of the stratum corneum in the form of a continuous layer, and the exogenous EMR particles are in the spatial arrangement of the particles corresponding to the lattice of optical isolated points in the tissue. 242. The method of claim 237, wherein the method is heated by a plurality of EMR beams delivering the same. 205. A method according to any one of claims 200 to 214, wherein the device is the device of any one of claims 1-199. A method for selectively damaging a portion of a subject's tissue, comprising:
Applying EMR radiation to a part of the subject's tissue, creating a grid of EMR-treated isolated points in the part of the tissue,
A method whereby the EMR process isolated point absorbs an amount of EMR that is sufficient to damage tissue within the EMR process isolated point but not sufficient to cause significant tissue damage. A method for selectively damaging a portion of a subject's tissue, comprising:
Processing a part of the subject's tissue with an EMR processing device that creates a grid of EMR processing isolated points in the part of the tissue,
A method whereby the EMR process isolated point absorbs an amount of EMR that is sufficient to damage tissue within the EMR process isolated point, but insufficient to cause significant tissue damage. 245. The method of claim 244, wherein the damage comprises clotting or denaturation of intracellular or extracellular proteins within the EMR treated isolated point. 245. The method of claim 244, wherein the damage includes evaporation of water within the EMR processing isolated point. 245. The method of claim 244, wherein the damage comprises killing cells within the EMR treated isolated point. 245. The method of claim 244, wherein the damage comprises tissue detachment within the EMR processing isolated point. 245. The method of claim 244, wherein the EMR-treated isolated point grid is heated to a temperature of 35-40 ° C. 254. The method of claim 244, wherein the grid of EMR treated isolated points is heated to a temperature of 40-50 ° C. 245. The method of claim 244, wherein the EMR-treated isolated point grid is heated to a temperature of 50-100 ° C. 245. The method of claim 244, wherein the EMR treated isolated point grid is heated to a temperature of 100-200C. 245. The method of claim 244, wherein the EMR treated isolated point grid is heated to a temperature greater than 200C. 245. The method of claim 244, wherein the grid of EMR-processed isolated points comprises a multiplicity of isolated points, each isolated point having a maximum dimension of 1 μm to 30 nm. 245. The method of claim 244, wherein the grid of EMR-processed isolated points comprises isolated point multiplicity with each isolated point having a maximum dimension of 1 μm to 10 μm. 245. The method of claim 244, wherein the EMR-processed isolated point grid comprises isolated point multiplicity with each isolated point having a maximum dimension of 10 μm to 100 μm. 245. The method of claim 244, wherein the grid of EMR treated isolated points comprises a multiplicity of isolated points, each isolated point having a maximum dimension of 100 μm to 1 mm. 245. The method of claim 244, wherein the grid of EMR-processed isolated points comprises isolated point multiplicity with each isolated point having a maximum dimension of 1 mm to 10 mm. 245. The method of claim 244, wherein the grid of EMR treated isolated points has a fill factor of 0.01-90%. 245. The method of claim 244, wherein the grid of EMR treated isolated points has a fill factor of 0.01-0.1%. 245. The method of claim 244, wherein the grid of EMR treated isolated points has a fill factor of 0.1-1%. 245. The method of claim 244, wherein the grid of EMR treated isolated points has a fill factor of 1-10%. 245. The method of claim 244, wherein the grid of EMR treated isolated points has a fill factor of 10-30%. 245. The method of claim 244, wherein the grid of EMR treated isolated points has a fill factor of 30-50%. 245. The method of claim 244, wherein the EMR treated isolated point is a thermal isolated point having a minimum depth from the tissue surface of 0-4 mm. 268. The method of claim 265, wherein the EMR process isolated point has a minimum depth from the tissue surface of 0-50 [mu] m. 268. The method of claim 265, wherein the EMR process isolated point has a minimum depth from the tissue surface of 50-500 [mu] m. 268. The method of claim 265, wherein the EMR process isolated point has a minimum depth from the tissue surface of 500 μm to 4 mm. 269. The method of any one of claims 265-268, further comprising cooling the surface of the tissue to prevent the formation of thermal isolated points on the surface. 269. The method of any one of claims 265-268, further comprising cooling the surface of the tissue to prevent formation of a thermal isolation point from the surface to the minimum depth. A part of the tissue is warts,
245. The method of claim 244, wherein the wart tissue is damaged by creating a grid of the EMR treated isolated points. A part of the tissue is an octopus;
245. The method of claim 244, wherein the octopus tissue is damaged by creating a grid of the EMR treated isolated points. A portion of the tissue is a sweat gland;
245. The method of claim 244, wherein the sweat gland tissue is damaged by creating a grid of the EMR treated isolated points. The sweat glands are associated with body odor,
276. The method of claim 276, wherein the body odor is reduced by damaging the sebaceous gland tissue. A portion of the tissue is psoriatic plaque;
245. The method of claim 244, wherein the psoriatic plaque tissue is damaged by creating a grid of the EMR treated isolated points. A part of the tissue is a sebaceous gland,
245. The method of claim 244, wherein the sebaceous gland tissue is damaged by creating a grid of the EMR treated isolated points. The sebaceous glands are associated with acne scars,
276. The method of claim 276, wherein the acne scar is reduced by damaging the sebaceous gland tissue. A portion of the tissue is adipose tissue;
245. The method of claim 244, wherein the adipose tissue is damaged by creating a grid of the EMR treated isolated points. The adipose tissue is associated with cellulite;
278. The method of claim 278, wherein the cellulite is reduced by damaging the adipose tissue. A method for reducing skin pigmentation in a subject comprising:
Treating a portion of the subject's skin with an EMR processor that creates a grid of EMR isolated points in at least one volume of tissue containing the pigment;
Destroying the dye without killing cells containing the dye thereby. A method for reducing skin pigmentation in a subject comprising:
Treating a portion of the subject's skin with an EMR processor that creates a grid of EMR isolated points in at least one volume of tissue containing the pigment;
Thereby destroying cells containing said dye. 281. The method of claim 280 or 281, wherein the pigment is present in a tattoo, port wine nevus, nevus or buckwheat. A method for photodynamic treatment of a subject in need of photodynamic treatment comprising:
Processing a portion of the subject's tissue with an EMR processor that creates a grid of EMR isolated points within the desired treatment area of the subject;
Whereby the EMR treatment comprises activating a photodynamic agent present in the isolated point. 284. The method of claim 283, wherein the photodynamic agent is administered to the subject prior to the treatment. 284. The method of claim 283, wherein the photodynamic agent is selected from the group consisting of an antitumor agent and psoralen.